1. NAM required more visits and longer overall duration compared with TIO. 2. The center employing IO showed favorable nasolabial esthetics compared to those not utilizing IO. 3. No significant differences were found in the nasolabial esthetics of patients who have received NAM compared with TIO.

The centers that used NAM and other forms of PSOT did not have better dental arch relationships or craniofacial morphology compared with the centers that performed only primary lip repair. However, this study was not designed to investigate the cause-and-effect relationship between specific outcomes and particular features of those protocols.

The purpose of this investigation was to determine reliability and validity of GOSLON Yardstick ratings using plaster casts versus photo galleries of digital images in actual intercenter comparisons. The dental arch relationships of 112 patients with complete unilateral cleft lip and palate from 3 North American cleft/craniofacial centers were rated in 2 separate studies. In the first, plaster casts were used. For a later intercenter comparison, the same dental casts were scanned, digital bases added, and two-dimensional photographic galleries (6 views) were created for each set of casts. Three raters experienced with the GOSLON Yardstick carried out 2 separate ratings of the plaster casts in the first study, then of the photographic gallery of scanned digital images of the same casts in the second study. Inter- and intrarater reliabilities were calculated using the Weighted Kappa statistic. Average scores for each patient were calculated and compared between methods with correlation statistics and a Bland-Altman plot. Kruskal-Wallis test was used to compare results between centers using both media. Reliability using both methods was very good and comparable between methods. Mean weighted Kappas were: inter-rater = 0.815 (plaster) versus 0.891 (photo); and intrarater = 0.866 (plaster) versus 0.891 (photo). There was a highly significant correlation (r = 0.920). Mean difference between centers was 0.033 of a GOSLON category. The level of significance of the differences found between centers with both methods was identical, confirming the interchangeability of both media presentations.

Identifying populations at risk of SLE who remain unaffected would provide insights for potential disease prevention. Using a unique resource of SLE patient family members, first degree relatives (FDRs) of SLE patients (n = 154) with plasma samples available from previous genetic studies and who remained unaffected at follow-up evaluation (mean time = 6.8 years) were matched to healthy individuals unrelated to SLE patients (Controls). FDRs and Controls provided clinical and demographic information, and completed screening questionairres at baseline (BL) and follow-up (FU). BL and FU plasma samples were assessed for autoantibody production and soluble mediators. FDRs had significantly higher BL and FU CSQ scores (p<0.0001), but no difference in the number of positive autoantibodies compared to Controls. FDRs had significant (p < 0.01) increases in 38 (of 52) soluble mediators at BL and FU, including IFN-associated chemokines, TNFR ligands, and regulatory mediators (p<0.002). Levels of MIP-1α (p=0.008), MIG (p=0.019), GROα (p=0.001), ICAM-1 (p=0.007), and VEGF (p=0.004), along with CSQ scores (p=0.010), best distinguished FDRs from Controls in logistic regression models. These alterations are present despite lack of progression to classified SLE, suggesting that multiple perturbations in immune-mediated inflammatory processes present in FDRs of SLE patients may be offset by inhibitory factors.

Spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders caused by a number of different mutations the leads to loss of motor coordination with characteristic ages of onset, symptomatology, and rates of progression. SCA type 34 (SCA34) is an age-related cerebellar neurodegenerative disorder caused by mutations in the Fatty Acid Elongase-4 (ELOVL4). The ELOVL4 is an essential enzyme that mediates biosynthesis of Very Long Chain Saturated and Polyunsaturated Fatty Acids (VLC-SFA and VLC-PUFA, resp., ≥28 carbons) that are critical for the normal function of brain, skin, retina, Meibomian glands, and testes in which ELOVL4 is expressed. Global deletion or homozygous expression of truncated mutant ELOVL4 that lack VLC-SFA and VLC-PUFA biosynthesis cause severe skin disorders, seizures and neonatal mortality in rodents and humans. To understand the consequences of ELOVL4 mutations in pathogenesis of SCA34, we generated a rat model of SCA34 by knock-in of the SCA34-causing 736T>G (p.W246G) ELOVL4 mutation. We show that heterozygous and homozygous rats carrying the W246G mutation developed impaired motor deficits by two months of age. Our electrophysiological studies using cerebellar slices found marked reduction of long-term potentiation at parallel fiber synapses and long-term depression at climbing fiber synapses onto Purkinje cells in the homozygous W246G mutant rats. Our results further point to ELOVL4 products as being essential for motor function and cerebellar synaptic plasticity. These results suggest that in SCA34 patients, ataxia likely arises from primary impairment of synaptic plasticity and cerebellar network desynchronization that precedes cerebellar degeneration and loss of motor coordination with aging.