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Background: Sepofarsen is an RNA antisense oligonucleotide (AON) targeting the common c.2991+1655A>G mutation in the CEP290 gene to treat Leber congenital amaurosis type 10 (LCA10), a condition with severe childhood-onset vision loss or blindness. Methods: In this 12-month, multicenter, open-label, multiple-dose, dose-escalation, phase 1b/2 trial, patients with LCA10 received up to four doses of intravitreal sepofarsen in the worse-seeing eye. Primary end point was safety; secondary end points included vision outcome measures. Findings: Of 11 patients enrolled (8–44 years of age), six received loading/maintenance doses of sepofarsen of 160 µg/80 µg and five received 320 µg/160 µg. Reported cases of cataracts, mild cystoid macular edema, and retinal thinning were 3, 0, and 0, respectively, in the 160-µg/80-µg group and 5, 2, and 2 in the 320-µg/160-µg group. Pooled data (n=11) showed improvements from baseline to Month 12 in treated eyes vs untreated eyes in mean ± standard error of the mean best-corrected visual acuity (BCVA: −0·55 ± 0·26 vs −0·12 ± 0·07 logarithm of the minimum angle of resolution [logMAR], p

Aims We examined the risk association between single nucleotide polymorphisms (SNPs) in eleven candidate genes with type 2 diabetes (T2D). T2D-associated polymorphisms were also examined for prediction of incident CHD. Methods 113 tagging SNPs were genotyped in stage 1 (467 T2D cases, 290 controls), and 15 SNPs were analyzed in the final cohort (1462 T2D cases, 600 controls). Three T2D-associated SNPs were further tested for prediction of CHD within a subset of 1417 T2D cases free of CHD at enrolment. Results In the case–control analysis, PPARG rs1801282 (Pro12Ala) (OR = 1.48 (1.02–2.16)), ADIPOQ rs1063539 (OR = 1.17 (1.01–1.35)), and HNF4A rs1884614 (OR = 1.16 (1.00–1.32) were associated with T2D (Pallelic

A series of substituted naphthyl containing chiral [2.2.1] bicycloheptanes were prepared utilizing asymmetric Diels-Alder chemistry. This paper describes structure-activity relationships in this series. The N-methyl 2-naphthyl analogue (16d) and its desmethyl analogue (17d) are active triple re-uptake inhibitors both in vivo and in vitro. (C) 2003 Elsevier Ltd. All rights reserved.

We report a genomewide linkage study of type 2 diabetes (T2D [MIM 125853]) in the Icelandic population. A list of type 2 diabetics was cross-matched with a computerized genealogical database clustering 763 type 2 diabetics into 227 families. The diabetic patients and their relatives were genotyped with 906 microsatellite markers. A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 2.90, P=1.29 x 10(-4)) in all diabetics. Since obesity, here defined as body mass index (BMI)or =30 kg/m(2), is a key risk factor for the development of T2D, we studied the data either independently of BMI or by stratifying the patient group as obese (BMIor =30) or nonobese (BMI30). A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 3.64, P=2.12 x (10)-5) in the nonobese diabetics. No linkage was observed in this region for the obese diabetics. Linkage analysis conditioning on maternal transmission to the nonobese diabetics resulted in a LOD score of 3.48 (P=3.12 x 10(-5)) in the same region, whereas conditioning on paternal transmission led to a substantial drop in the LOD score. Finally, we observed potential interactions between the 5q locus and two T2D susceptibility loci, previously mapped in other populations.

African American women have been considered a double jeopardy due to being both Black and female. The existing literature does not offer research on African American women wealth builders as there is very little research on various subjects on African American women. This study of the motivation and success strategies of African American women wealth builders in the $100K Club sought to bridge the gap in literature. The purpose of this research was to explore the lived experiences of 20 African American women wealth builders who have savings of at least $100K regarding their motivation and success strategies. A semi structured interview was designed to capture the lived experiences of these African American women as they described what motivated them, how they saved at least $100K of earned income, and who or what contributed to their successes and failures along the way. The data was entered into a Microsoft Excel spreadsheet that was used to analyze the data to provide textural data, patterns, and themes. This study examined the financial strategies participants used during their financial growth. The findings of this study revealed the participants’ saving strategies of financial plans, 401[k]s, deferred comp., real estate investments, investment retirement accounts, stock portfolios, savings accounts, and company matched programs.