The strictly regulated expression of most pleiotropic developmental control genes is critically dependent on the activity of long-range cis-regulatory elements. This was revealed by the identification of individuals with a genetic condition lacking coding-region mutations in the gene commonly associated with the disease but having a variety of nearby chromosomal abnormalities, collectively described as cis-ruption disease cases. The congenital eye malformation aniridia is caused by haploinsufficiency of the developmental regulator PAX6. We discovered a de novo point mutation in an ultraconserved cis-element located 150 kb downstream from PAX6 in an affected individual with intact coding region and chromosomal locus. The element SIMO acts as a strong enhancer in developing ocular structures. The mutation disrupts an autoregulatory PAX6 binding site, causing loss of enhancer activity, resulting in defective maintenance of PAX6 expression. These findings reveal a distinct regulatory mechanism for genetic disease by disruption of an autoregulatory feedback loop critical for maintenance of gene expression through development.

IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

Improved health-related quality of life (HRQOL) and reduced activity limitations are prime objectives of migraine therapy, but no data on the effect of preventive treatments on these outcomes are available. We monitored changes in HRQOL using the Short Form 36 (SF-36) and headache-related activity limitations using the Migraine Disability Assessment Score (MIDAS) in 141 consecutive migraine without aura patients on prophylaxis. A total of 102 patients completed the 3-month study. Mean (SD) number of headache days/month dropped from 8.0 (3.7) to 5.0 (2.3) (P < 0.001). Mean monthly consumption of acute drugs reduced from 7.4 (3.5) to 4.4 (3.1) (P < 0.001). MIDAS total score reduced (improved) significantly. All SF-36 scale scores increased (improved), most significantly. This first study to assess prospectively the impact of prophylaxis on HRQOL and daily activities in a large series indicates that migraine prophylaxis has the potential to reduce the global burden of migraine on individuals and society.

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Objective.Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years.Methods.Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics.Results.Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.Conclusion.At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

The standard parameters considered to compare energy-harvesting efficiency such as the efficiency measured in standard test conditions or the concept of peak Watt power production may lead to an incorrect estimation of the real producible energy. In this work, we aim to confirm that in realistic outdoor building-integrated photovoltaic (BIPV) installations, the gap between dye-sensitized solar cells (DSC) and other available technologies is lower than expected in terms of producible energy. We have developed a model for the evaluation of the producible energy on a generic BIPV site with DSC technology. Average daily irradiation and temperature are considered to integrate the instantaneous power to obtain the energy production. To compare the producible energy of DSC technology with other commercial photovoltaic technologies (crystalline and amorphous silicon, CdTe, or copper indium gallium selenide), we use the estimation of energy production available under the Photovoltaic Geographical Information System platform

In our patients, the risk of uveitis was related to younger age at onset of arthritis and presence of ANA, but not to female sex and disease category. This finding suggests that the patients who require the most intensive ophthalmologic screening are those who have early-onset JIA and are ANA-positive, regardless of their sex or disease subtype.