Chronological Age Research Articles

Bone age and dental late effects in childhood cancer survivors: Radiographic findings in a Brazilian sample.

Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination. To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors. This is a retrospective case-control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5-15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%. The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region. Close multidisciplinary collaboration is necessary during the follow-up period of young patients who have survived cancer.

Bringing Self-Determination Theory to the Forefront: Examining How Human Resource Practices Motivate Employees of All Ages to Succeed

AbstractSelf-determination theory (SDT) is widely used in human resource (HR) practice studies to explain how HR practices impact work outcomes. However, there is little empirical evidence establishing the complete SDT mediational process in the HR domain, which entails basic psychological needs and motivation acting as mediators of relations between HR practices and work outcomes. The present study addresses this issue with a mixed methods approach. Using an item classification task with subject matter experts (N = 48), HR practices were classified as autonomy-, competence-, and relatedness-supportive. Based on this scheme, we tested an SDT-based conceptual model in a three-wave sample of working adults (N = 818). Results from Multilevel Structural Equation Modeling (MSEM) support the hypothesized model: basic psychological need satisfaction and autonomous motivation mediate the relationship between HR practice perceptions and work outcomes (performance, thriving, affective organizational commitment, and turnover intentions). Autonomy-supportive practices had a positive effect on autonomy need satisfaction, while competence-supportive practices had positive associations with all three basic psychological needs. Counterintuitively, relatedness-supportive practices had negative effects on autonomy and competence need satisfaction, and the relationship between relatedness-supportive practices and autonomy need satisfaction was moderated by chronological age. We discuss our findings in the context of prominent HR studies that utilize SDT and offer a supplemental age-inclusive HR practice scheme for HR managers interested in understanding the benefits of supporting basic psychological needs from both a motivation and workforce retention standpoint.

Methscore: a comprehensive R function for DNA methylation-based health predictors.

DNA methylation-based predictors of various biological metrics have been widely published and are becoming valuable tools in epidemiologic studies of epigenetics and personalized medicine. However, generating these predictors from original source software and web servers is complex and time consuming. Furthermore, different predictors were often derived based on data from different types of arrays, where array differences and batch effects can make predictors difficult to compare across studies. We integrate these published methods into a single R function to produce 158 previously published predictors for chronological age, biological age, exposures, lifestyle traits and serum protein levels using both classical and principal component-based methods. To mitigate batch and array differences, we also provide a modified RCP method (ref-RCP) that normalize input DNA methylation data to reference data prior to estimation. Evaluations in real datasets show that this approach improves estimate precision and comparability across studies. The function was included in software package ENmix, and is freely available from Bioconductor website (https://www.bioconductor.org/packages/release/bioc/html/ENmix.html). Supplementary data are available at Bioinformatics online.

Association between biological aging and diabetic retinopathy

The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06–1.18) and PA (OR = 1.11, 95% CI, 1.07–1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99–1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR.

Abstract PS03-09: Age-related normal breast tissue features differ in women with germline BRCA1/2 mutations

Abstract Ageing, a breast cancer risk factor, can be reflected in histologically normal breast tissue (NBT). However, the relationship between age-related histological features and cancer risk is not fully understood. We propose that biological and microscopic features can be identified in seemingly histologically NBT in gBRCA1/2m carriers that are indicative of the earliest tissue changes of breast cancer, potentially as a result of accelerated tissue ageing. To study NBT, we have put in place a unique and scalable repository, named OASIS, storing currently >2,000 digitised whole slide images (WSI) of H&E-stained NBT from individuals with long clinical follow-up. These tissues are from individuals with a spectrum of risk for developing breast cancer and derived from reduction surgery from non-gBRCA1/2m carriers, risk reducing masectomies, and from contralateral and peri-tumoural NBT from gBRCA1/2m carriers and women with breast cancer. Across 6 NBT resources, 70 selected WSIs were manually annotated for epithelial cells, fibrous stroma and adipocytes, resembling the "ground truth". Extensive comparisons of different tile sizes, tile overlapping ratios, stain normalisation techniques and deep learning (DL) feature extractors were conducted to implement a Tissue-Classifier, which achieved 95% accuracy in 3-fold cross-validation. Based on the MobileNet architecture, a DL-framework achieved a sensitivity of 81.2% and specificity of 81.8% (84.7% AUC) in predicting Tissue-Age based on discernible histological patterns in healthy women. In gBRCA1/2m carriers, we discovered features of accelerated tissue ageing (e.g. degree of lobule involution), indicating that the biological NBT age differs from their chronological age. Our DL-based framework robustly captured histological patterns to predict tissue components and age. The global organisation of these patterns showed variations in WSIs of women with different risks of developing breast cancers, which may provide new insights into premalignant alterations in NBT. Citation Format: Anita Grigoriadis, Mario Parreno-Centeno, Siyuan Chen, Gregory Verghese, Esther Lips, Cheryl Gillett, Louise Jones, Sarah Pinder. Age-related normal breast tissue features differ in women with germline BRCA1/2 mutations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS03-09.

Dentální a skeletální indikátory růstového spurtu v ortodoncii

Aim: The aim was to confirm the correlation between chronological age, skeletal age according to X-ray picture of the hand and wrist, and the stages of teeth development, and to determine whether the assessment of teeth development can be used to establish the stage of growth of an individual. Material and method: 362 adolescents were included in the study; 180 boys between the age 11.5–15.5, 182 girls between the age 10.5–14.5. To assess teeth in OPG Demirjian’s classification was used. We assessed teeth 43, 44, 45 and 47 in the mandible, and 13, 14, 15, 17 and 18 in the maxilla. To assess radiographs of the hand and wrist Björk, Grave and Brown classification was applied. Results: The correlation of skeletal and dental age was proved. The highest correlation was found in lower permanent canine, both in girls and boys. S-stage in radiograph of the hand (the stage prior to the maximum growth spurt) corresponds to the stage of the lower canine root with parallel walls (G-stage according to Demirjian). Thus, in case OPG of lower permanent canine shows parallel walls of the root canal the maximum of growth spurt occurs within 0.5–1 year. The maximum growth spurt (MP3cap stage) and the following stages correspond to the situation when lower canine apex is closed (H-stage according to Demirjian). This can help us in the correct timing of orthodontic treatment. ORTODONCIE | ročník 33 | č. 2/2024 ODBORNÉ PRÁCE / ORGINAL ARTICLES Recenzovaný časopis České ortodontické společnosti 14 Conclusion: The assessment of the developmental stages of teeth, namely lower permanent canine, is used in the planning of orthodontic treatment, and can serve as

Accuracy of Age Estimation Method Using Dental Radiographs of Permanent Mandibular Second Molars in a Southern Thailand Population

Age estimation is an important process for identifying individuals. In 2020, Duangto et al. estimated age by assessing dental development according to the method of Demirjian on permanent mandibular second molars using a panoramic radiograph. They also developed equations and tested their accuracy in a population of northern Thailand. However, several studies have shown that age estimation methods vary in suitability and accuracy depending on genetic and environmental factors within each population group. Therefore, this research aimed to test the accuracy of dental age estimation using the equations derived from panoramic radiographs of permanent mandibular second molars in a population of southern Thailand. A total of 224 radiographs of 112 males and 112 females aged 7–14 years were used for this study. The samples were categorized into eight groups (28 radiographs per group). The study identified tooth development in stages C–G that followed the Demirjian method and converted these stages into numerical values (3–7). The researchers tested these numerical values in the Duangto et al. equations. The findings revealed that age estimation using the Duangto et al. equations was not significantly different from chronological age. The accuracy had a margin of error not exceeding one year with 95% confidence intervals. In conclusion, the age estimation equations of Duangto et al. can accurately estimate the age of persons living in southern Thailand.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study

ObjectiveTo (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic...

Cerebrospinal fluid proteomic profile of frailty: Results from the PROLIPHYC cohort.

Frailty is a clinical state reflecting a decrease in physiological reserve capacities, known to affect numerous biological pathways and is associated with health issues, including neurodegenerative diseases. However, how global protein expression is affected in the central nervous system in frail subject remains underexplored. In this post hoc cross-sectional biomarker analysis, we included 90 adults (52-85 years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers of neurodegenerative diseases. We investigated the human proteomic profile of cerebrospinal fluid associated with frailty defined by an established cumulated frailty index (FI, average = 0.32), not enriched for neurology clinical features. Using a label-free quantitative proteomic approach, we identified and quantified 999 proteins of which 13 were positively associated with frailty. Pathway analysis with the top positively frailty-associated proteins revealed enrichment for proteins related to inflammation and immune response. Among the 60 proteins negatively associated with frailty, functional pathways enriched included neurogenesis, synaptogenesis and neuronal guidance. We constructed a frailty prediction model using ridge regression with 932 standardized proteins. Our results showed that the "proteomic model" could become an equivalent predictor of FI in order to study chronological age. This study represents the first comprehensive exploration of the proteomic profile of frailty within cerebrospinal fluid. It sheds light on the physiopathology of frailty, particularly highlighting processes of neuroinflammation and inhibition of neurogenesis. Our findings unveil a range of biological mechanisms that are dysregulated in frailty, in NPH subjects at risk of neurodegenerative impairment, offering new perspectives on frailty phenotyping and prediction.

Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

The age of leadership: Meta‐analytic findings on the relationship between leader age and perceived leadership style and the moderating role of culture and industry type

AbstractManagers' leadership style has a substantial impact on employee and organizational outcomes. In the present study, we consider the role of leaders’ chronological age in predicting followers’ perceptions of their leadership style. Whereas ample research uncovers relationships between individuals’ age and how these individuals are perceived by others, little is known about how leaders’ chronological age impacts others’ perceptions of their style. Even less is known about how such relationships vary across cultures and industries. We conducted a meta‐analysis (164 unique studies; N = 397,456 observations) to explore these relationships, using the Full‐Range leadership model. We found that leader age was negatively related to perceptions of transformational and transactional leadership, and positively related to perceptions of passive leadership. Further, some of these effects varied on several cultural dimensions: The negative relationship between leader age and transformational leadership was weaker in collectivistic cultures, while the negative relationship with transactional leadership was stronger in high power distance cultures. Industry type also mattered: the relationship between leader age and both transformational and contingent reward leadership styles was amplified in the public sector. Lastly, perceptions of older leaders were more negative when ratings were provided by followers rather than the leaders themselves. Our findings offer both theoretical and practical implications for leading in an increasingly age‐diverse workforce, such as better informing the workforce of present age stereotypes and their imminent effect on organizations.

Evaluation of The Relationship Between Dental and Cervical Vertebrae Maturation in Terms of Age Determination

Aim: Age determination is a very important issue in anthropology, forensic science, and dentistry. Today, the most commonly used methods for age determination are the methods in which tooth and bone development are evaluated. This study aims to evaluate the relationship between gender, chronological age, dental maturation, and cervical vertebral maturation in individuals aged 8-25 years. Material and Method: Digital panoramic, lateral cephalometric radiographs of 500 patients aged 8-25 years were used in this study. Cervical vertebra maturation was evaluated using the dental maturation-modified Demirjian classification system of Baccetti et al. Means, minimum, maximum, and standard deviations were calculated and analyzed as descriptive statistics. Kolmogorov-Smirnov, Kappa, Kruskal-Wallis, Chi-Square, Linear Regression, and Spearman Correlation tests were used for statistical analysis. Results: There was a statistically significant difference between chronological age and dental maturation and cervical vertebral maturation levels (p <0.01). While dental maturation levels did not differ significantly according to gender (p> 0.05), cervical vertebra maturation was statistically different (p <0.01). There was a positive correlation between chronological age and dental maturation, and cervical vertebral maturation levels (p <0.01). There was a strong correlation between dental maturation and cervical vertebral maturation levels (p <0.01). Conclusion: The findings of this study showed that skeletal maturity increased with the increase in chronological and dental age for both genders. The earlier formation was consistently observed for each stage of skeletal maturation in females. All correlations between skeletal and dental maturations were statistically significant.

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study.

Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Associations of combined phenotypic aging and genetic risk with incident cancer: A prospective cohort study

Background:Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.Methods:Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).Results:Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p&lt;0.001; Beta = –0.98 in women, p&lt;0.001).Conclusions:Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.Funding:This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).

Evaluation of the Effect of Medications Used in Children with Rheumatic Diseases on Dental Maturation.

The study's main objective is to compare dental maturation in healthy children and those with rheumatic diseases. It also aims to determine the age of children with Pediatric Rheumatic Diseases (PRD), specifically focusing on comparing those receiving medical treatment to those who are not, and to differentiate between biological and non-biological medication recipients, to identify potential differences. This observational cross-sectional study was conducted to assess the dental maturation stages in a cohort of 278 children (126 boys, 152 girls) aged between 6 and 14 years between September 2021 and December 2023. The study population included individuals with PRD requiring dental treatment and systemically healthy children. Digital panoramic radiographs were utilized for the evaluation of dental maturation in both groups. A statistically perfect agreement was found among the dental age (DA) calculated by the researchers (ICC=1.000; p&lt;0.01). A statistically perfect level of agreement was found between the chronological age (CA) of the cases and the DA measured by the Willems method (ICC=0.921; p&lt;0.01). It was found that the difference between the estimated DA and CA was higher in girls and boys in the PRD group who were taking medication. No significant differences were found in DA estimated based on gender and treatment status among individuals with PRD. The Willems method tended to underestimate the age of girls receiving biological treatment while overestimating the age in all other groups.

Short- and long-term predictive power of the preoperative Geriatric Assessment components in older patients undergoing cholecystectomy.

Introduction: Increasing numbers of older patients will require laparoscopic cholecystectomies. Physicians may have doubts when qualifying these patients for elective surgeries, since older age is considered a risk factor for complications. Determining biological age, using a Geriatric Assessment (GA), should be the key factor in the preoperative assessment. The goal of this study was to determine which GA components are most useful for predicting postoperative outcomes in both short- and long-term follow-up.Materials and Methods: 219 consecutive patients aged ≥70 years underwent surgery and were followed-up prospectively for 12 months. The preoperative GA consisted of functionality, physical activity, comorbidity, polypharmacotherapy, nutrition, cognition, mood, and social support domain. Logistic regression analyses were used to analyse the predictive ability of the GA. Results: GA, frailty and chronological age were not predictive of major 30-day morbidity. There were significantly more overall postoperative complications in the frail group, mainly minor and medical. There were no significant differences in the rate of major and surgical complications between frail and fit patients. Only frailty was a predictor of 1-year mortality. Conclusion: Performing GA before elective laparoscopic cholecystectomies seems unnecessary for the evaluation of short-term outcomes but helpful for the assessment of long-term outcomes. Laparoscopic cholecystectomy can be safely performed also in older frail patients.

Gene-Environment Interactions and Gene-Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants.

PhenoAge and BioAge are two commonly used biological age (BA) measures. The author here searched for gene-environment interactions (GxE) and gene-gene interactions (GxG) on PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 111,996 Taiwan Biobank (TWB) participants, including a discovery set of 86,536 TWB2 individuals and a replication set of 25,460 TWB1 individuals. Searching for variance quantitative trait loci (vQTLs) provides a convenient way to evaluate GxE and GxG. A total of 4 nearly independent (linkage disequilibrium measure r2 < 0.01) PhenoAgeAccel-vQTLs are identified from 5,303,039 autosomal TWB2 SNPs (p < 5E-8), whereas no vQTLs are found from BioAgeAccel. These 4 PhenoAgeAccel-vQTLs (rs35276921, rs141927875, rs10903013, and rs76038336) are further replicated by TWB1 (p < 5E-8). They are located in the OR51B5, FAM234A, and AXIN1 genes. All 4 PhenoAgeAccel-vQTLs are significantly associated with PhenoAgeAccel (p < 5E-8). A phylogenetic heat map of the GxE analyses showed that smoking exacerbated the PhenoAgeAccel-vQTLs' aging effects, while higher educational attainment attenuated the PhenoAgeAccel-vQTLs' aging effects. Body mass index, chronological age, alcohol consumption, and sex do not prominently modulate PhenoAgeAccel-vQTLs' aging effects. Based on these vQTL results, rs141927875-rs35276921 interaction (p = 4.7E-61) and rs76038336-rs10903013 interaction (p = 3.3E-116) on PhenoAgeAccel are detected.

Handwriting difficulties in children with dyslexia: Poorer legibility in dictation and alphabet tasks, slowness in the alphabet task.

Several studies have shown that children with dyslexia (DYS), in addition to their reading and spelling deficits, encounter handwriting difficulties that are still poorly understood in terms of their nature and origin. The present study aimed to better understand the handwriting difficulties of children with DYS by comparing their handwriting quality and speed in two tasks, a dictation task and an alphabet task, which required fewer spelling skills than the dictation task. Twenty-nine French-speaking children (Mage = 9.5 years) participated in the study, including 18 children with DYS and nine typically developing (TD) children matched on chronological age. The children performed control tasks, a dictation task with words varying in graphic and orthographic complexity and an alphabet writing task. Accuracy, handwriting quality (legibility), and fluency (speed, writing and pause time) were carefully measured using a digital tablet. GLMM analysis and t tests showed that children with DYS made more aesthetic errors (handwriting quality) in both the dictation and alphabet task than TD children. They also wrote more slowly than TD children in the alphabet task (speed, pause time). These findings suggest that children with DYS present handwriting difficulties, even in a simple alphabet task. In dictation, they seem to favour speed at the expense of handwriting quality.

Unstimulated Luteinizing Hormone for Assessment of Suppression During Treatment of Central Precocious Puberty with 6-Month Subcutaneous Leuprolide Acetate: Correlations with Clinical Response.

Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. Aims of this secondary analysis: evaluate unstimulated luteinizing hormone (LH) as efficacy measure; assess clinical suppression metrics; and present biochemical and clinical data for subgroups not achieving hormone suppression. 62 children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH). 84% and 86% of children achieved unstimulated LH&lt;1IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH&lt;1IU/L at week 24 that completed the study, all showed lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH&lt;4IU/L at week 24 and 48 (AUC=0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3cm. Of 7 girls not achieving stimulated LH&lt;4IU/L at week 24, all achieved E2&lt;10pg/mL, showed lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH&lt;1IU/L. Unstimulated LH has value as an efficacy measure and concentrations &lt;1IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.

Epigenetic Aging Associations With Psychoneurological Symptoms and Social Functioning in Adults With Sickle Cell Disease.

Objective: Sickle cell disease (SCD), the most common inherited blood disorder in the United States, is associated with severe psychoneurological symptoms. While epigenetic age acceleration has been linked to psychoneurological symptom burden in other diseases, this connection is unexplored in SCD. This study aimed to assess the association between epigenetic age acceleration and psychoneurological symptom burden in SCD. Methods: In this cross-sectional study, emotional impact, pain impact, sleep impact, social functioning, and cognitive function were assessed in 87 adults living with SCD. DNA methylation data were generated from blood specimens and used to calculate epigenetic age using five clocks (Horvath, Hannum, PhenoAge, GrimAge, & DunedinPACE). Associations between epigenetic age acceleration and symptoms were assessed. Results: The sample (N = 87) had a mean (SD) chronologic age was 30.6 (8.1) years. Epigenetic age acceleration was associated with several symptom outcomes. GrimAge age acceleration (β = -0.49, p = .03) and increased DunedinPACE (β = -2.23, p = .004) were associated with worse emotional impact scores. PhenoAge (β = -0.32, p = .04) and the GrimAge (β = -0.48, p = .05) age acceleration were associated with worse pain impact scores. Increased DunedinPACE (β = -2.07 p = .04) were associated with worse sleep impact scores. Increased DunedinPACE (β = -2.87, p = .005) was associated with worse social functioning scores. We did not find associations between epigenetic age acceleration and cognitive function in this sample. Conclusion: Epigenetic age acceleration was associated with worse symptom experiences, suggesting the potential for epigenetic age acceleration as a biomarker to aid in risk stratification or targets for intervention to mitigate symptom burden in SCD.