Age Gap Research Articles

Prognostic assessment based on the trajectory of artificial intelligence-enabled electrocardiograms for age estimation

Abstract Background Artificial Intelligence (AI) estimation of age using data from the 12-lead electrocardiogram (ECG) has demonstrated its utility as a biomarker in predicting the future risk of cardiac diseases and mortality. However, expected long-term outcomes based on temporal changes in the AI-ECG age gap remain unclear. Purpose This study aims to utilize the difference between ages predicted by AI-ECG and actual ages longitudinally for follow-up and to assess whether there are significant clinical differences in mortality among specific groups. Methods Among patients at a hospital who had not been used for the AI-ECG age prediction model (121,702 individuals, 522,261 ECGs), 6,685 individuals with 31,858 ECGs who had an index ECG and the subsequent ECG in the fifth year, with at least one intervening ECG were included for analysis. The absolute age gap, defined as the absolute difference between ECG-predicted and chronological age, was limited to ±10 for analysis. Latent class trajectory modeling was then utilized to classify groups based on the AI-ECG age gap. Results Data-driven analysis revealed four distinct trajectory groups based on age gap trajectories: Consistently Young ECG (27.2%), Reversed ECG Aging (35.3%), Accelerated ECG Aging (8.0%), and Consistently Old ECG (29.5%). Notably, the Accelerated ECG Aging group exhibited a significantly higher cumulative incidence of all-cause death (adjusted hazard ratio (HR) 1.66 (95% confidence interval (CI) 1.30-2.12, p-value <0.001) and non-cardiac death (adjusted HR 1.83 (95% CI 1.38-2.43, p-value <0.001) compared to the Consistently Young ECG group. Conclusion Among 4 distinct trajectories based on the changes in the AI-ECG age gap, Accelerated ECG Aging was associated with a heightened risk of all-cause mortality. Additional in-depth analysis of factors associated with Accelerated ECG Aging is warranted.

Investigating socioeconomic disparities in prescribing new diabetes medication

Abstract Background There is a concern regarding socioeconomic disparities in prescription of new medications such as SGLT-2is or GLP-1RAs in type 2 diabetes mellitus (T2DM). This study aims to analyze prescription patterns of these medications and assess socioeconomic disparities in their initiation among individuals with T2DM with very high cardiovascular risk. Methods Individuals diagnosed with T2DM and very high cardiovascular risk were identified (N = 10,768) based on general practitioner’ electronic health record data. Socioeconomic status (SES) was based on standardized disposable household income in quintiles. The association between SES and the prescription of SGLT-2is and GLP-1RAs in 2022 was investigated by logistic regression analyses, adjusting for potential confounding factors. SGLT-2is and GLP-1RAs prescription patterns were examined over 2019-2022, stratified for age-groups and sex. Results We found a positive association between SES quintile 1 (referent) and quintile 4 in SGLT-2is prescription in all models (OR 1.29 95%CI:1.08-1.54 in the fully adjusted model). For prescriptions of GLP-1RAs, we found no significant differences in SES. Proportionally, men are more frequently prescribed SGLT-2is, while there are no sex disparities in GLP-1RAs prescription. Older individuals consistently receive fewer SGLT-2is and GLP-1RAs prescriptions compared to other age categories. Conclusions We observed sex and age disparities but no profound socioeconomic differences in initiation of SGLT-2is and GLP-1RAs in the Netherlands. The latter may be due to guidelines’ clear indication of the eligible population (T2DM and very high cardiovascular risk) and GP education. Future development and potential disparities in initiation and maintenance should be monitored. Key messages • We found no disparities in prescribing new Type 2 diabetes medication based on socioeconomic status. • The adoption of prescribing new medication for Type 2 diabetes patients takes time.

How family businesses transfer their values across generation: a conceptual framework

Purpose Recognising the value of sustaining virtuous values in family business across generations, this paper aims to provide a conceptual framework and propose a mediated-moderated mechanism through which family members’ traits, such as family size and parenting style, influence the extent to which family business’s virtuous values transfer across generations. Design/methodology/approach The paper is based on systematic literature that was conducted using specific keyword searches in the business source databases of Emerald, ProQuest, ScienceDirect, EBSCOhost and SpringerLink. Findings This paper leads to a conceptual framework proposing a mediating relationship between family members’ traits and the transfer of virtuous values to the next generation. Further, two parallel mediators are proposed, moderated by traits of family members’ offspring, such as the age gap and gender of offspring. Research limitations/implications This paper proposes a conceptual framework focusing on transferring virtuous values across generations in the family business. It investigates family members’ traits, such as the size of the family and parenting style, to comprehend the family members’ traits and the transfer of virtuous values relationship. Practical implications The proposed conceptual framework should form the basis of interventions adopted by family business members to enhance the transfer to virtuous values across generations by positively impacting their moral self-efficacy and affective commitment to virtuous values. Originality/value Prior research on family businesses has primarily explored transgenerational succession. However, sustaining virtuous values across generations is equally important to retain a business’s legacy. Very limited scholarly attention has focused on these virtuous values in family business.

Utilization of modern contraceptives and associated factors among women of homeless reproductive age in Adama town, Oromia, Ethiopia

BackgroundFamily planning refers to a conscious effort by a couple to limit or space the number of children they have through the use of contraceptive methods. Contraceptive utilization is a practice that helps individuals or couples avoid unwanted pregnancy. A lack of family planning puts homeless individuals at a higher risk of unwanted pregnancies and sexually transmitted infections. However, there is little data about modern contraceptive utilization among homeless women in the study area.ObjectivesIt has aimed to assess the utilization of modern contraceptives and associated factors among homeless reproductive-age women in Adama town, 2023.MethodsA community-based cross-sectional study was conducted in Adama town among 286 homeless women. A convenience sampling technique was used. The data were collected through face-to-face interviews using a pretested structured questionnaire. The collected data were cleaned, coded, and entered into Epi Info, and the data were exported to the Statistical Package for Social Sciences (SPSS) version 22. Descriptive statistics were used to characterize the study population. The associations between dependent and independent variables were modeled using binary logistic regression. The adjusted odds ratio (AOR) and 95% confidence interval (CI) were used to estimate associations, and a P value < 0.05 was considered to indicate statistical significance.ResultsOut of the planned 289 respondents, 286 (98.9%) were participated. The prevalence of modern contraceptive utilization was 56.6% [95% CI: (50.7, 62.2)]. Among the utilizers, implants (52.5%), injectables (42%), and pills (5.5%) were used. Homeless women aged 25–34 years [AOR = 4.22, 95% CI: (1.77, 10.05)], a formal education [AOR = 3.04, 95% CI: (1.21, 7.60)], a slept off-street [AOR = 2.81, 95% CI: (1.25, 6.34)], a monthly income greater than or equal to 2400 Ethiopian birr [AOR = 4.18, 95% CI: (2.11, 8.29)], a sexual intercourse AOR = 3.14, 95% CI: (1.17, 8.40)], and a history of pregnancy after joining the street life [AOR = 9.21, 95% CI: (3.67, 23.12)] were factors significantly associated with the utilization of modern contraceptives.ConclusionThe prevalence of modern contraceptive utilization among homeless women was relatively higher than in previous studies. The associated factors for contraceptive utilization included age, education, place for sleeping, income, sexual intercourse and history of pregnancy after joining the street life. The Regional and Adama town Health Bureau and facilities should develop targeted interventions (considering age, educational, and other disparities) to reduce the unmet need for modern contraception and halt unnecessary health outcomes among homeless women, their children, and families.

A multi-center retrospective cohort analysis of age and racial disparities in patients undergoing repeat ablation for recurrent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, and its prevalence has been increasing worldwide. Current data shows that AF is more common in white males compared to blacks despite blacks having multiple cardiovascular comorbidities. There is paucity of data showing the recurrence of AF re-ablation after index ablation specifically as it pertains to race, gender, and age. We sought to explore the rates of recurrent AF re-ablation in this retrospective cohort analysis. Methods Using a multi-center database, we examined 23,558 encounters and 10,530 had readmission records i.e. readmitted within 3 years. The encounters included adults (18+) who had an ablation procedure for atrial fibrillation between 1/1/2018-06/30/2020. We used binary logistic regression models and Tukey-Kramer procedure to analyze pairwise comparisons among different subgroups of race, sex, and age group. The primary endpoint was recurrence of repeat ablation. Secondary endpoints included non-fatal stroke and myocardial infarction. Results Our sample size was 23,558 patients, 20,276 were white patients (86%) and 3,282 were non-white patients (14%). The average age was 66.29 years (SD 10.43) and average age at the time of repeat ablation was 65.97 years. The average BMI was 21.55. Out of the 23,558 patients, 14.30% (N= 3368) had re-ablation within 3 years of the index ablation. The odds ratio of re-ablation for patients in their 50s is 1.4229 (95% CI [1.1172, 1.8122]) compared to patients in their 80s. Similarly, the odds ratio is 1.4330 (95% CI [1.1466, 1.7909]) for the 60-69 group, 1.3075 (95%CI [1.0458, 1.6346]) for the 70-79 group and 1.3443 (95% CI [1.0088, 1.7914]) for patients below 50 compared to over 80 group. The LR for re-ablation was 0.8438 (p=0.3583) in females. The incidence of non-fatal stroke and MI were 0.27% (N= 63) and 0.19% (N= 45). Average length of time to re-ablation was 415.5 days. Discussion When controlling for age group and sex, race was not significantly associated with an increased likelihood of repeat ablation. When controlling for race and age group, sex was not significantly associated with an increased likelihood of repeat ablation. When controlling for race only, females were not at a higher risk of re-ablation. However, when controlling for race and sex, patients in their 50s are 42.3% more likely to have re-ablation when compared to patients in their 80s. In contrast, the age of patients at their first ablation increased, there appeared to be a rising trend indicating a higher chance of AF recurrence within 3 years when controlling for race and sex. Conclusion The incidence of repeat AF ablation is not higher in racial minorities when compared to whites. Interestingly, there appears to be an decreasing rate of AF re-ablation in older patients despite a higher rate of AF recurrence as age increases possibly owing to more conservative therapeutic approach such as medical management.

Disentangled Lifespan Synthesis via Transformer‐Based Nonlinear Regression

AbstractLifespan face age transformation aims to generate facial images that accurately depict an individual's appearance at different age stages. This task is highly challenging due to the need for reasonable changes in facial features while preserving identity characteristics. Existing methods tend to synthesize unsatisfactory results, such as entangled facial attributes and low identity preservation, especially when dealing with large age gaps. Furthermore, over‐manipulating the style vector may deviate it from the latent space and damage image quality. To address these issues, this paper introduces a novel nonlinear regression model‐Disentangled Lifespan face Aging (DL‐Aging) to achieve high‐quality age transformation images. Specifically, we propose an age modulation encoder to extract age‐related multi‐scale facial features as key and value, and use the reconstructed style vector of the image as the query. The multi‐head cross‐attention in the W+ space is utilized to update the query for aging image reconstruction iteratively. This nonlinear transformation enables the model to learn a more disentangled mode of transformation, which is crucial for alleviating facial attribute entanglement. Additionally, we introduce a W+ space age regularization term to prevent excessive manipulation of the style vector and ensure it remains within the W+ space during transformation, thereby improving generation quality and aging accuracy. Extensive qualitative and quantitative experiments demonstrate that the proposed DL‐Aging outperforms state‐of‐the‐art methods regarding aging accuracy, image quality, attribute disentanglement, and identity preservation, especially for large age gaps.

“An Algorithm for Public Service Media?” Embedding Public Service Values in the News Recommender System on RTBF's Platform

In a rapidly evolving digital landscape, public service media (PSM) face a significant challenge: how to leverage recommendation algorithms to enhance their visibility and attractiveness without sacrificing their core values. This study examines the extent to which the Belgian Radio-Television of the French Community (RTBF) has integrated PSM values into the development of a recommender system for news articles on its platform (rtbf.be). The research highlights a conscientious effort to define and translate PSM values before the algorithm design phase, both inside and outside the organization. However, the study also reveals limitations that hinder the full realization of PSM values within the recommender system. Consequently, these values currently function more as abstract guiding principles and communication tools than tangible technical features. The study emphasizes the challenge of reconciling public service ethos with algorithmic realities and concludes by highlighting the need for further empirical research to bridge this gap in the digital age.

A review of artificial intelligence-based brain age estimation and its applications for related diseases.

The study of brain age has emerged over the past decade, aiming to estimate a person's age based on brain imaging scans. Ideally, predicted brain age should match chronological age in healthy individuals. However, brain structure and function change in the presence of brain-related diseases. Consequently, brain age also changes in affected individuals, making the brain age gap (BAG)-the difference between brain age and chronological age-a potential biomarker for brain health, early screening, and identifying age-related cognitive decline and disorders. With the recent successes of artificial intelligence in healthcare, it is essential to track the latest advancements and highlight promising directions. This review paper presents recent machine learning techniques used in brain age estimation (BAE) studies. Typically, BAE models involve developing a machine learning regression model to capture age-related variations in brain structure from imaging scans of healthy individuals and automatically predict brain age for new subjects. The process also involves estimating BAG as a measure of brain health. While we discuss recent clinical applications of BAE methods, we also review studies of biological age that can be integrated into BAE research. Finally, we point out the current limitations of BAE's studies.

Brain predicted age in chronic pelvic pain: a study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network.

The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted - chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average-however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.

Association between allostatic load and accelerated white matter brain aging: findings from the UK biobank.

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29years in association analysis and by 0.33years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.

Social status, chaste widowhood, and trends in marital age gaps in post-Imjin Korea, 1606–1630

Social status, chaste widowhood, and trends in marital age gaps in post-Imjin Korea, 1606–1630

Epidemiology and regional variance of traumatic peripheral nerve injuries in Sweden: A 15-year observational study.

Traumatic peripheral nerve injuries pose significant challenges to healthcare systems and individuals, affecting sensory function, causing neuropathic pain, and impairing quality of life. Despite their impact, comprehensive studies on the epidemiology and regional variance of these injuries are scarce. Understanding the incidence, trends, and anatomical distribution of such injuries is essential for targeted interventions and resource allocation. This observational study utilized register-based data from the Swedish National Patient Register covering the period from 2008 to 2022. Incidence rates, trends, and anatomical distribution of traumatic peripheral nerve injuries were analyzed using descriptive statistics, Poisson regression modeling, and regional comparisons. Higher incidences of peripheral nerve injuries were observed among men compared to women across all age groups. The hand and wrist were the most commonly affected sites. Regional variations in incidence rates were evident, with some regions consistently exhibiting higher rates compared to others. Notably, a decreasing trend in injuries was observed over the study period. This study underscores the importance of targeted interventions and preventive strategies, considering sex, age, and regional disparities. Further research incorporating individual patient-level data is warranted to enhance our understanding and inform tailored interventions to reduce the burden of these injuries.

Advanced ECG Heart Age: A Prognostic, Explainable Machine Learning Approach Applicable to Sinus and Non-Sinus Rhythms

Abstract Background An explainable advanced electrocardiography (A-ECG) Heart Age gap is the difference between A-ECG Heart Age and chronological age. This gap is an estimate of accelerated cardiovascular ageing expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG Heart Age requires sinus rhythm. Aims To develop and prognostically validate a revised, explainable A-ECG Heart Age applicable to both sinus and non-sinus rhythms. Methods An A-ECG Heart Age excluding P-wave measures was derived from the 10-second 12-lead ECG in a derivation cohort using multivariable regression machine learning with Bayesian 5-minute 12-lead A-ECG Heart Age as reference. The Heart Age was externally validated in a separate cohort of patients referred for cardiovascular magnetic resonance imaging by describing its association with heart failure hospitalization or death using Cox regression, and its association with comorbidities. Results In the derivation cohort (n=2771), A-ECG Heart Age agreed with the 5-min Heart Age (R2=0.91, bias 0.0±6.7 years), and increased with increasing co-morbidity. In the validation cohort (n=731, mean age 54±15 years, 43% female, n=139 events over 5.7 [4.8–6.7] years follow-up), increased A-ECG Heart Age gap (≥10 years) associated with events (hazard ratio [95% confidence interval] 2.04 [1.38–3.00], C-statistic 0.58 [0.54–0.62], and the presence of hypertension, diabetes mellitus, hypercholesterolemia, and heart failure (p≤0.009 for all). Conclusions An explainable A-ECG Heart Age gap applicable to both sinus and non-sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival.

Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021.

Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI). In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = -0.8, P < 0.0001), rabies (r = -0.7, P < 0.0001), HIV/AIDS (r = -0.6, P < 0.0001), COVID-19 (r = -0.5, P < 0.0001), dengue (r = -0.4, P < 0.0001), and EVD (r = -0.2, P < 0.005). VIDPs pose major public health challenges worldwide, with significant regional, age, and gender disparities. The results underscore the need for targeted interventions and international cooperation to mitigate the burden of these diseases. Policymakers can use these findings to implement cost-effective interventions and improve health outcomes, particularly in regions with high or increasing burdens.

8789 Unraveling Von Hippel Lindau Syndrome: A Comprehensive Analysis of Clinical Manifestations, Age-Related Variations, and Tumor Prevalence in a Specialized Endocrine Center

Abstract Disclosure: K.K. Pasam: None. Y. Gupta: None. A. Goyal: None. N. Tandon: None. Introduction: This study presents a thorough examination of Von Hippel Lindau (VHL) syndromes, focusing on the clinical spectrum and genetic mutations in our population. Methods: The study, conducted at the Department of Endocrinology and Metabolism from 2016 to 2022. Objectives included studying the spectrum of diseases in index patients and asymptomatic family members. Results: In our study, we identified 19 index cases and 12 asymptomatic cases identified on screening. The analysis of 31 VHL patients revealed a mean age of presentation of 24.2±11.1 years. Pancreatic cysts were the most common manifestation in 61% followed by pheochromocytoma in 54%, cerebellar hemangioblastomas in 45%, retinal angiomas in 39% and renal cell carcinoma in 35%. 16% of patients presented with nonfunctioning pancreatic neuroendocrine tumors, and one case featured an endolymphatic sac tumor.Pheochromocytomas in VHL syndrome presented at a remarkably young age, with an average of 23.1±11.4 years. Bilateral pheochromocytomas were observed in 14 (82%) and hormonal evaluation revealed urinary noradrenaline, normetanephrines, and plasma normetanephrine elevations of 5, 6, and 7-fold, respectively.The median size of pheochromocytomas in VHL syndrome was 5.4 cm. Metastatic pheochromocytoma was observed in one patient. Genetic analysis was available for 9 patients with most common mutation in exon 3 of chromosome 3. Discussion:The average age of VHL syndrome presentation in our cohort is younger than in other Indian studies. Males in our study were 45%, deviating from the absence of gender preponderance associated with VHL. Disparities in age of diagnosis and tumor prevalence compared with other international cohorts highlight potential regional and ethnic variations. Multiple pancreatic cysts in our study, with a prevalence of 61%, lower than the South Indian study's 71%. Literature comparisons indicate pancreatic cyst prevalence ranging from 42% to 51.6%. Cerebellar hemangioblastomas and retinal angiomas, typical VHL lesions, displayed prevalence rates of 45% and 39%, respectively.Pheochromocytoma, the second most common tumor in our cohort (54%), exhibited variations in prevalence compared to international studies. Higher rates reported by Fagundes et al. and Dwivedi et al. from Brazil might be attributed to recruitment biases from endocrine centers.The average age of VHL-associated pheochromocytoma presentation in our study contrasts with MEN2, emphasizing the unique features of VHL. Our study, reporting a 16% prevalence of PNETs, aligns with Binderup et al. The mean age of presentation for VHL-associated PNETs (20.8 ± 3.63 years) contrasts with Western literature, suggesting potential ethnic differences. Conclusion: Our study contributes to a nuanced understanding of VHL syndrome, shedding light on age-related variations, gender distribution, and tumor prevalence. Presentation: 6/2/2024

8789 Unraveling Von Hippel Lindau Syndrome: A Comprehensive Analysis Of Clinical Manifestations, Age-Related Variations, And Tumor Prevalence In A Specialized Endocrine Center

Abstract Disclosure: K.K. Pasam: None. Y. Gupta: None. A. Goyal: None. N. Tandon: None. Introduction: This study presents a thorough examination of Von Hippel Lindau (VHL) syndromes, focusing on the clinical spectrum and genetic mutations in our population. Methods: The study, conducted at the Department of Endocrinology and Metabolism from 2016 to 2022. Objectives included studying the spectrum of diseases in index patients and asymptomatic family members. Results: In our study, we identified 19 index cases and 12 asymptomatic cases identified on screening. The analysis of 31 VHL patients revealed a mean age of presentation of 24.2±11.1 years. Pancreatic cysts were the most common manifestation in 61% followed by pheochromocytoma in 54%, cerebellar hemangioblastomas in 45%, retinal angiomas in 39% and renal cell carcinoma in 35%. 16% of patients presented with nonfunctioning pancreatic neuroendocrine tumors, and one case featured an endolymphatic sac tumor.Pheochromocytomas in VHL syndrome presented at a remarkably young age, with an average of 23.1±11.4 years. Bilateral pheochromocytomas were observed in 14 (82%) and hormonal evaluation revealed urinary noradrenaline, normetanephrines, and plasma normetanephrine elevations of 5, 6, and 7-fold, respectively.The median size of pheochromocytomas in VHL syndrome was 5.4 cm. Metastatic pheochromocytoma was observed in one patient. Genetic analysis was available for 9 patients with most common mutation in exon 3 of chromosome 3. Discussion:The average age of VHL syndrome presentation in our cohort is younger than in other Indian studies. Males in our study were 45%, deviating from the absence of gender preponderance associated with VHL. Disparities in age of diagnosis and tumor prevalence compared with other international cohorts highlight potential regional and ethnic variations. Multiple pancreatic cysts in our study, with a prevalence of 61%, lower than the South Indian study's 71%. Literature comparisons indicate pancreatic cyst prevalence ranging from 42% to 51.6%. Cerebellar hemangioblastomas and retinal angiomas, typical VHL lesions, displayed prevalence rates of 45% and 39%, respectively.Pheochromocytoma, the second most common tumor in our cohort (54%), exhibited variations in prevalence compared to international studies. Higher rates reported by Fagundes et al. and Dwivedi et al. from Brazil might be attributed to recruitment biases from endocrine centers.The average age of VHL-associated pheochromocytoma presentation in our study contrasts with MEN2, emphasizing the unique features of VHL. Our study, reporting a 16% prevalence of PNETs, aligns with Binderup et al. The mean age of presentation for VHL-associated PNETs (20.8 ± 3.63 years) contrasts with Western literature, suggesting potential ethnic differences. Conclusion: Our study contributes to a nuanced understanding of VHL syndrome, shedding light on age-related variations, gender distribution, and tumor prevalence. Presentation: 6/2/2024

6681 Age and Sex Disparity in NASH and the Potential Role of Estradiol Treatment for NASH

Abstract Disclosure: M. Tripathi: None. S. Sakthivel: None. A. Suzuki: None. B.K. Singh: None. P.M. Yen: None. Introduction: NAFLD (nonalcoholic fatty liver disease) and its more severe form, NASH (nonalcoholic steatohepatitis) are sexually dimorphic conditions that exhibit higher prevalence in men than women during reproductive ages but have similar prevalence after menopause. Reproductive age women are protected from hepatic fibrosis relative to men, although they lose this protection after menopause. These sex differences in NASH have been attributed, at least partly, to different circulating estrogen levels. However, the underlying mechanism(s) is not fully understood. We thus conducted animal experiments to investigate: 1) sex differences in the histologic severity of NASH, necroinflammatory and fibrogenic activities, and other relevant pathways in young and old male and female mice and 2) the effects of estradiol administration on these parameters in old male and female mice to evaluate the therapeutic potential of estradiol in NASH. Methodology: Young/reproductive age (12-weeks old) and old/post-reproductive age female and male (48∼50-weeks weeks old) C57BL/6J mice were fed control chow diet (NCD) or high-fat methionine/choline-deficient (MCD) diet for six weeks to induce NASH. The old mice were administered 200nM 17β-estradiol (physiological) in drinking water. We analyzed serum and hepatic NASH parameters, ER stress, and lysosome-autophagy defects. Results and Conclusion: Among reproductive age mice with NASH, females developed less severe histologic inflammation and fibrosis and decreased gene expression of Il1b, Il6, Tgfb, Col1a1, Ccl2, and Ccl5, and lower hepatic collagen than males. Females with NASH also had less inhibition of hepatic autophagy and lysosomal protein expression than males with NASH. Among old mice, post-reproductive age females fed NCD or MCD exhibited more severe hepatic inflammation and fibrosis and had higher gene expression of inflammatory and fibrogenic markers with comparable autophagic inhibition and lysosomal defects as similar age males. Physiological doses of estradiol significantly reduced hepatic gene expression of inflammatory and fibrogenic markers, ER stress and lysosomal-autophagic defects in post-reproductive age females. In conclusion, similar to clinical NASH, we observed marked sex and age-related differences in the severity of NASH. Furthermore, physiological doses of estradiol treatment improved the hepatic histology, lysosome-autophagy, inflammation, and fibrosis in post-reproductive age female mice with NASH and suggests that estradiol supplementation may decrease or reverse NASH progression in post-menopausal women with NASH. Presentation: 6/2/2024

The effect of atomoxetine efficacy on freezing of gait in patient with Parkinson’s disease: a double-blinded randomized clinical trial

Introduction: Freezing of gait (FOG) is a debilitating symptom experienced by many individuals with Parkinson’s disease, characterized by an abrupt and transient inability to initiate or continue locomotion. Despite extensive research, effective pharmacological interventions targeting FOG remain elusive. Atomoxetine, a selective norepinephrine reuptake inhibitor, has shown promise in alleviating FOG in small-scale studies. However, the efficacy of atomoxetine in larger cohorts remains underexplored. Objectives: This study aims to assess the impact of atomoxetine on Parkinson’s disease-related FOG in a larger study population than currently reported in the literature. Patients and Methods: This randomized clinical trial was performed in Golestan Hospital, Ahvaz, Iran, in 2022. The participants were divided into group A comprising 16 patients subjected to atomoxetine treatment, and group B consisting of 16 patients administered a placebo. Three scheduled visits were conducted. Freezing of Gait Questionnaire (FOGQ) scores was documented during each visit. Results: The mean age of all participants was 62.4 ± 8.3 years, with no significant intergroup age disparity and no statistically significant gender-based distinctions between the two groups. The average disease duration in the atomoxetine group was 8.2 ± 3.1 years, while in the placebo group, it was 7.2 ± 3.4 years, with no significant divergence between the two groups. The study findings indicated no significant distinction in FOGQ scores between the treatment and placebo groups. Conclusion: Though atomoxetine did not significantly improve improvement in freezing of the gait of studied patients with Parkinson’s disease, it may cause a modest improvement in the gait freezing of some patients. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20211008052695N1; https://irct.behdasht.gov.ir/trial/59643, ethical code; #IR.AJUMS.HGOLESTAN. REC.1400.026).

Exploration of oral hygiene practices, oral health status, and related quality of life of individuals residing in the Rorya district of Tanzania, East Africa.

Oral health substantially impacts individuals' quality of life, making it an important target for global health interventions. This research describes oral health status, practices, and beliefs within the Rorya district of Tanzania to understand barriers to care. To quantify physical oral health status, intraoral examinations were conducted on adults, noting the Decayed Missing and Filled Teeth (DMFT) and Comprehensive Periodontal Inflammatory Burden Index (CPBI). Oral Health-Related Quality of Life (OHRQoL) and semi-structured interviews were conducted to understand oral hygiene behaviors and beliefs. Data was analyzed via two-sample t-tests, Pearson's statistics, and NVIVO. A purposive sample (n = 139) of participants self-reported to reside in either Burere (n = 32), Nyambogo (n = 52), or Roche (n = 55) were assessed. A two-sample t-test revealed females (n = 67; x¯ = 7.1; SD = 5.4; p < 0.05) have a significantly higher DMFT score than males (n = 72; x¯ = 3.7; SD = 3.9). Moreover, the OHRQoL score of females (n = 67; x¯ = 12.10; SD = 14; p < 0.05) were significantly higher than males (n = 72; x¯ = 10.16; SD = 3). In contrast, males have significantly higher CPBI scores (x¯ = 3.8; SD = 1.5; p=<0.05) than females (x¯ = 3.0; SD = 1.3). Additionally, older age groups presented higher GI and PISA scores, while the younger group (20-30 years) displayed the highest mean DMFT score. The themes that emerged from semi-structured interviews were "pearls of laughter guarded by wisdom teeth," "whispered tales of oral tides and communal echoes," and "tales of the tooth fairy." In this community, proper oral health maintenance techniques are vital yet frequently disregarded, mainly due to disparities in access to resources, reflected in oral health scores. Addressing this is a crucial intervention, presenting an opportunity to uplift overall well-being. Moreover, gender and age disparities in oral health highlight the urgent need for tailored interventions.

Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.

The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.