The functionality of African-specific variants in the TGFB1 regulatory region and their potential role in HIVAN.

Background: Transcription of transforming growth factor beta-1 (TGF-β1) is regulated by a polymorphic promoter region containing African-specific single nucleotide polymorphisms (SNPs). Some of these SNPs have higher frequencies among Southern Africans compared to other African populations and their functionality has only been partially studied. Due to the high prevalence of HIV-associated nephropathy (HIVAN) in Africans we hypothesized that functional African TGFB1-promoter SNPs may contribute to HIVAN pathogenesis.

The African-387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis.

Although extraocular muscles are commonly affected by myasthenia gravis (MG) at presentation, a treatment-resistant ophthalmoplegic complication of MG (OP-MG) occurs in younger patients with African-genetic ancestry. In MG, pathogenic antibodies activate complement-mediated muscle damage and this may be potentiated in some OP-MG cases because of relative deficiency of decay-accelerating factor/CD55. Extending this argument, we hypothesized that OP-MG individuals may harbor African-specific polymorphisms in key genes influencing extraocular muscle remodeling.

The prevalence of pain at home and its consequences in children following two types of short stay surgery: a multicenter observational cohort study.

Background: The potential for pain at home in children following day case surgery has long been recognized. Pain has also been associated with behavioral disturbances and sleep disruption in children following surgery and may also impact negatively on recovery, parental and patient satisfaction, family life, healthcare use, and have an economic cost.

Aim: To investigate the prevalence of pain at home, and its consequences, in children following two types of short stay surgery across eight pediatric centers in the UK in an observational cohort study.

Non-negative matrix factorization for learning alignment-specific models of protein evolution.

Models of protein evolution currently come in two flavors: generalist and specialist. Generalist models (e.g.

Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P1 and S1P5.

The optimization of a series of thiazolopyridine S1P1 agonists with limited activity at the S1P3 receptor is reported. These efforts resulted in the discovery of 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo-[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P1/S1P5 agonist with limited activity at S1P3 and no activity at S1P2/S1P4. Dosed orally at 0.