Incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis.

PURPOSE: To investigate the population-based incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis. METHODS: Patients newly diagnosed with Marfan syndrome in Olmsted County, Minnesota, from January 1, 1976, through December 31, 2005, were identified through medical records review. Outcome measures were Marfan incidence, de novo mutation rate, risk of ectopia lentis. RESULTS: Marfan syndrome was identified in 17 patients during the 30-year period, yielding an incidence of 0.52 per 100,000 people/year (95% CI, 0.27-0.77). Mean age at diagnosis was 24.4 years (range, 1.7 year to 51.3 years). Nine patients (53%) were female. Of the 17, 5 (29%) were new mutations, with a calculated mutation rate of 3.8 ± 1.7 × 10-5. Four (24%) were diagnosed with ectopia lentis, including 3 at the time of their Marfan diagnosis. Of the 14 patients at risk for developing ectopia lentis after being diagnosed with Marfan syndrome, 1 (7%) developed it during a mean follow-up of 9 years (range, 0-6.4). Twelve (71%) were diagnosed with dilated ascending aorta during a mean follow-up of 13.2 years (range, 6.7 months to 28.9 years). CONCLUSIONS: Incidence and de novo mutation rate of Marfan syndrome in this population-based cohort was higher than prior reports. Ectopia lentis, whose prevalence in North America has not been reported previously, occurred in approximately one-fourth of study patients and more commonly around the time of initial Marfan diagnosis.

Stanniocalcin-1 is a Modifier of Oxygen-Induced Retinopathy Severity.

Purpose/Aim: Abnormal activation of signaling pathways related to angiogenesis, inflammation, and oxidative stress has been implicated in the pathophysiology of retinopathy of prematurity (ROP), a leading cause of blindness in pre-term infants. Therapies for ROP include laser and anti-vascular endothelial growth factor agents. However, these therapies have side effects, and even with adequate treatment, visual acuity can be impaired. Novel therapeutic options are needed. Stanniocalcin-1 (STC-1) is a neuroprotective protein with anti-inflammatory and anti-oxidative stress properties. Rodent models of oxygen-induced retinopathy (OIR) were selected to determine whether STC-1 plays a role in the development of OIR.Materials and methods: STC-1 gene and protein expression was first evaluated in the Sprague Dawley rat OIR model that is most similar to human ROP. OIR was then induced in wild-type and Stc-1-/- mice. Retinas were isolated and evaluated for avascular and neovascular area on retinal flat mounts. Quantification of gene expression by quantitative real-time PCR was performed. VEGF was assayed by ELISA in media obtained from induced pluripotent stem-cell-derived retinal pigment epithelial (iPS-RPE) cells following treatment with recombinant STC-1.Results: STC-1 was significantly upregulated in a rat model of OIR compared to room air controls at the gene (P < .05) and protein (P < .001) level. Stc-1-/- OIR mice showed significantly worse ROP compared to wild-type mice as assessed by avascular (20.2 ± 2.4% vs 15.2 ± 2.5%; P = .02) and neovascular area (14.3 ± 2.7% vs 8.8 ± 3.7%; P < .05). Transcript levels of vascular endothelial growth factor-A were significantly higher in Stc-1-/- OIR mice compared to wild-type controls (P = .03). STC-1 reduced VEGF production in iPS-RPE cells (P = .01).Conclusions: STC-1 plays a role in the OIR stress response and development of pathologic vascular features in rodent OIR models by regulating VEGF levels.

Recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common acute oral ulcerative condition in North America. RAS is divided into a mild, common form, simple aphthosis, and a severe, less common form, complex aphthosis. Aphthosis is a reactive condition. The lesions of RAS can represent the mucosal manifestation of a variety of conditions. These include conditions with oral and genital aphthae such as ulcus vulvae acutum, reactive nonsexually related acute genital ulcers, and Behçet disease. The mouth is the beginning of the gastrointestinal (GI) tract, and the lesions of RAS can be a manifestation of GI diseases such as gluten-sensitive enteropathy, ulcerative colitis, and Crohn disease. Complex aphthosis may also have correctable causes. The clinician should seek these in a careful evaluation. Successful management of both simple and complex aphthosis depends on accurate diagnosis, proper classification, recognition of provocative factors, and the identification of associated diseases. The outlook for patients with both simple and complex aphthosis is positive.

Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin.

BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. OBJECTIVE: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. DESIGN: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. RESULTS: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. CONCLUSION: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.