Unraveling Down Syndrome: From Genetic Anomaly to Artificial Intelligence-Enhanced Diagnosis.

Down syndrome arises from chromosomal non-disjunction during gametogenesis, resulting in an additional chromosome. This anomaly presents with intellectual impairment, growth limitations, and distinct facial features. Positive correlation exists between maternal age, particularly in advanced cases, and the global annual incidence is over 200,000 cases. Early interventions, including first and second-trimester screenings, have improved DS diagnosis and care. The manifestations of Down syndrome result from complex interactions between genetic factors linked to various health concerns. To explore recent advancements in Down syndrome research, we focus on the integration of artificial intelligence (AI) and machine learning (ML) technologies for improved diagnosis and management. Recent developments leverage AI and ML algorithms to detect subtle Down syndrome indicators across various data sources, including biological markers, facial traits, and medical images. These technologies offer potential enhancements in accuracy, particularly in cases complicated by cognitive impairments. Integration of AI and ML in Down syndrome diagnosis signifies a significant advancement in medical science. These tools hold promise for early detection, personalized treatment, and a deeper comprehension of the complex interplay between genetics and environmental factors. This review provides a comprehensive overview of neurodevelopmental and cognitive profiles, comorbidities, diagnosis, and management within the Down syndrome context. The utilization of AI and ML represents a transformative step toward enhancing early identification and tailored interventions for individuals with Down syndrome, ultimately improving their quality of life.

Central retinal vein occlusion after intense exercise: response to intravitreal bevacizumab.

A 40-year-old male athlete developed a central retinal vein occlusion after intense exercise and secondary dehydration. A comprehensive systemic evaluation was within the normal range. After a series of 11 intravitreal injections of bevacizumab over a 24-month period, spectral-domain optical coherence tomography showed resolution of macular edema with a 55-letter gain in visual acuity.

The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes.

Nr2e3 is an orphan nuclear receptor expressed specifically by retinal photoreceptor cells. Mutations in Nr2e3 result in syndromes characterized by excess blue cones and loss of rods: enhanced S-cone syndrome (ESCS) in humans and rd7 in mice. Using yeast two-hybrid screens with Nr2e3 as bait, the cone-rod homeobox protein Crx was identified as an interacting partner of Nr2e3. Immunoprecipitation assays confirmed this Nr2e3-Crx interaction and identified the DNA-binding domain of each protein as the interaction motif. Immunohistochemistry demonstrated that Crx and Nr2e3 are co-expressed by rod photoreceptors and their precursors. Chromatin immunoprecipitation assays on mouse retina demonstrated that Nr2e3 and Crx co-occupy the promoter/enhancer region of several rod and cone genes in the rod photoreceptor cells. The promoter/enhancer occupancy of Nr2e3 is Crx-dependent, suggesting that Nr2e3 is associated with photoreceptor gene targets by interacting with Crx. Transient transfection assays in HEK293 cells demonstrated that Nr2e3 enhances rhodopsin, but represses S- or M-cone opsin transcription when interacting with Crx. Quantitative real-time RT-PCR analysis on postnatal day 28 (P28) retina of the rd7 mouse, which lacks Nr2e3 protein, revealed an up-regulation of cone genes, but down-regulation of rod genes. Several mutant forms of human Nr2e3 identified from ESCS patients showed defects in interacting with Crx and/or in transcriptional regulatory function. Altogether, our findings suggest that Nr2e3 is a dual-function transcriptional regulator that acts in concert with Crx to promote and maintain the function of rod photoreceptors.