The Diagnostic Utility of Contrast-Enhanced FLAIR Imaging in the Diagnosis of Pediatric Uveitis.

Objectives: Contrast-enhanced FLAIR fat-suppressed (CE-FLAIR-FS) imaging can potentially increase the diagnostic accuracy of uveal diseases and ultimately provide better patient management. This study aimed to determine the diagnostic value of CE-FLAIR-FS imaging versus contrast-enhanced T1-weighted imaging (CE-T1WI) in the assessment of pediatric patients with uveitis. Material and methods: Twenty-one children with uveitis who underwent whole brain magnetic resonance imaging (MRI), including CE-FLAIR-FS and CE-T1WI, were retrospectively included in the study. We evaluated the presence of uveal tract contrast enhancement with thickening, vitreous humor signal abnormality, and accompanying brain abnormalities. The uveal enhancement intensity was assessed semiquantitatively as mild, moderate, and marked uveitis compared to CE-T1WI and CE-FLAIR-FS images. Results: Panuveitis (61.9%) was the most frequent anatomic location, and most of them were idiopathic (47.6%). Of the 42 eyes with clinical uveitis, enhancement of the uveal tract was observed on CE-FLAIR-FS images in 21 eyes (50%), while in 5 eyes (11.9%) on CE-T1WI. The sensitivity of CE-FLAIR-FS in panuveitis was detected to be quite high (80.8%). The number of affected eyes and enhancement degree were found to be higher on CE-FLAIR-FS (p < 0.001). In assessing the severity of uveitis, CE-FLAIR-FS grades were significantly higher and more sensitive than CE-T1WI (p < 0.001, Z: -4.347). Three patients had vitreous abnormal signals on CE-FLAIR-FS images, but none on CE-T1WI. Conclusion: CE-FLAIR-FS plays a significant role in the diagnosis of pediatric uveitis, identifying the involvement and severity of the uveal inflammation and guiding the appropriate management. It would be beneficial to add it as a standard sequence to the routine MRI protocol for uveal pathologies.

The DNA double-strand break repair proteins γH2AX, RAD51, BRCA1, RPA70, KU80, and XRCC4 exhibit follicle-specific expression differences in the postnatal mouse ovaries from early to older ages.

PURPOSE: Ovarian aging is closely related to a decrease in follicular reserve and oocyte quality. The precise molecular mechanisms underlying these reductions have yet to be fully elucidated. Herein, we examine spatiotemporal distribution of key proteins responsible for DNA double-strand break (DSB) repair in ovaries from early to older ages. Functional studies have shown that the γH2AX, RAD51, BRCA1, and RPA70 proteins play indispensable roles in HR-based repair pathway, while the KU80 and XRCC4 proteins are essential for successfully operating cNHEJ pathway. METHODS: Female Balb/C mice were divided into five groups as follows: Prepuberty (3 weeks old; n = 6), puberty (7 weeks old; n = 7), postpuberty (18 weeks old; n = 7), early aged (52 weeks old; n = 7), and late aged (60 weeks old; n = 7). The expression of DSB repair proteins, cellular senescence (ß-GAL) and apoptosis (cCASP3) markers was evaluated in the ovaries using immunohistochemistry. RESULT: ß-GAL and cCASP3 levels progressively increased from prepuberty to aged groups (P < 0.05). Notably, γH2AX levels varied in preantral and antral follicles among the groups (P < 0.05). In aged groups, RAD51, BRCA1, KU80, and XRCC4 levels increased (P < 0.05), while RPA70 levels decreased (P < 0.05) compared to the other groups. CONCLUSIONS: The observed alterations were primarily attributed to altered expression in oocytes and granulosa cells of the follicles and other ovarian cells. As a result, the findings indicate that these DSB repair proteins may play a role in the repair processes and even other related cellular events in ovarian cells from early to older ages.

The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection.

As women delay childbearing due to socioeconomic reasons, understanding molecular mechanisms decreasing oocyte quantity and quality during ovarian aging becomes increasingly important. The ovary undergoes biological aging at a higher pace when compared to other organs. As is known, telomeres play crucial roles in maintaining genomic integrity, and their shortening owing to increased reactive oxygen species, consecutive cellular divisions, genetic and epigenetic alterations is associated with loss of developmental competence of oocytes. Novel interventions such as antioxidant treatments and regulation of gene expression are being investigated to prevent or rescue telomere attrition and thereby oocyte aging. Herein, potential factors and molecular mechanisms causing telomere shortening in aging oocytes were comprehensively reviewed. For the purpose of extending reproductive lifespan, possible therapeutic interventions to protect telomere length were also discussed.

The crosstalk between telomeres and DNA repair mechanisms: an overview to mammalian somatic cells, germ cells, and preimplantation embryos.

Telomeres are located at the ends of linear chromosomes and play a critical role in maintaining genomic stability by preventing premature activation of DNA repair mechanisms. Because of exposure to various genotoxic agents, telomeres can undergo shortening and genetic changes. In mammalian cells, the basic DNA repair mechanisms, including base excision repair, nucleotide excision repair, double-strand break repair, and mismatch repair, function in repairing potential damages in telomeres. If these damages are not repaired correctly in time, the unfavorable results such as apoptosis, cell cycle arrest, and cancerous transition may occur. During lifespan, mammalian somatic cells, male and female germ cells, and preimplantation embryos experience a number of telomeric damages. Herein, we comprehensively reviewed the crosstalk between telomeres and the DNA repair mechanisms in the somatic cells, germ cells, and embryos. Infertility development resulting from possible defects in this crosstalk is also discussed in the light of existing studies.