From bimodal to unimodal: The transformed incidence of osteosarcoma in the United States.

Background: Osteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the SEER and NIS databases. Methods: Incidence rates of primary osteosarcoma between 2000-2021 were analyzed by age at diagnosis, year of occurrence, sex, and tumor site from the SEER Research Data, 17 Registries, Nov 2023 Sub (2000-2021). The incidence of cases in 35-64 year-olds and 65 and above was compared statistically to determine if there is an increased incidence in the later ages. Incidence of tumors of the long bones of the lower limbs from the NIS discharge database 2012-2019 was also analyzed for comparison. Results: Overall, 5,129 cases of osteosarcoma were reported in the SEER database. Across the 22 calendar year span, a consistent first peak appeared in the second decade of life. There was no consistent second peak in the 35+ age group. There were 86,100 discharges with long bone tumors analyzed in the NIS data which exhibited nearly identical patterns. Conclusions: Our analysis shows that the incidence of osteosarcoma is no longer bimodally distributed but rather unimodally distributed.

Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration: Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.

Mitochondrial Fatty Acid ß-Oxidation and Resveratrol Effect in Fibroblasts from Patients with Autism Spectrum Disorder.

Patients with autism spectrum disorder (ASD) may have an increase in blood acyl-carnitine (AC) concentrations indicating a mitochondrial fatty acid ß-oxidation (mtFAO) impairment. However, there are no data on systematic mtFAO analyses in ASD. We analyzed tritiated palmitate oxidation rates in fibroblasts from patients with ASD before and after resveratrol (RSV) treatment, according to methods used for the diagnosis of congenital defects in mtFAO. ASD participants (N = 10, 60%; male; mean age (SD) 7.4 (3.2) years) were divided in two age-equivalent groups based on the presence (N = 5) or absence (N = 5) of elevated blood AC levels. In addition, electron transport chain (ETC) activity in fibroblasts and muscle biopsies and clinical characteristics were compared between the ASD groups. Baseline fibroblast mtFAO was not significantly different in patients in comparison with control values. However, ASD patients with elevated AC exhibited significantly decreased mtFAO rates, muscle ETC complex II activity, and fibroblast ETC Complex II/III activity (p < 0.05), compared with patients without an AC signature. RSV significantly increased the mtFAO activity in all study groups (p = 0.001). The highest mtFAO changes in response to RSV were observed in fibroblasts from patients with more severe symptoms on the Social Responsiveness Scale total (p = 0.001) and Awareness, Cognition, Communication and Motivation subscales (all p < 0.01). These findings suggested recognition of an ASD patient subset characterized by an impaired mtFAO flux associated with abnormal blood AC. The study elucidated that RSV significantly increased fibroblast mtFAO irrespective of plasma AC status, and the highest changes to RSV effects on mtFAO were observed in the more severely affected patients.