Vossromero3346

Importance The effectiveness of afamelanotide treatment in patients with erythropoietic protoporphyria (EPP) in clinical practice who experience pain after light exposure that substantially impairs quality of life is unknown. Objective To evaluate the association of afamelanotide treatment with outcomes in patients with EPP in regular practice during longer-term follow-up. Design, Setting, and Participants This single-center, prospective postauthorization safety and efficacy cohort study was directed and approved by the European Medicines Agency. Data were collected from patients with EPP treated with afamelanotide at Erasmus MC between June 2016 and September 2018. Analysis began October 2018. Main Outcomes and Measures Time spent outside during treatment, number of phototoxic reactions, disease-specific quality of life, usage of protective clothing, and adverse events. Results A total of 117 patients with EPP (59 women [50.4%]; mean [SD] age, 43.0 [15.5] years) were treated with afamelanotide. Nearly all patients continued treatment (115 [98%]) with a median (interquartile range) follow-up of 2.0 (1.3-2.1) years. Compared with baseline, mean time spent outside during treatment increased significantly by an added 6.1 hours per week (95% CI, 3.62-8.67; P  less then  .001). Mean quality of life score improved significantly by 14.01% (95% CI, 4.53%-23.50%; P  less then  .001). Phototoxic reactions were less painful (β, -0.85; 95% CI, -1.43 to -0.26; P  less then  .001), but there was no significant difference in number or duration of reactions. Minor self-limiting adverse events occurred, such as nausea, fatigue, and headache. Conclusions and Relevance This cohort study found that afamelanotide treatment was associated with improved clinical outcomes and a good safety profile for patients with EPP. The treatment has clinically significant, sustained positive associations with quality of life, is associated with increased duration of sun exposure, and is associated with less severe phototoxic reactions.OBJECTIVE Data for the use of embedded performance validity tests (ePVTs) with multiple sclerosis (MS) patients are limited. see more The purpose of the current study was to determine whether ePVTs previously validated in other neurological samples perform similarly in an MS sample. METHODS In this retrospective study, the prevalence of below-criterion responding at different cut-off scores was calculated for each ePVT of interest among patients with MS who passed a stand-alone PVT. RESULTS Previously established PVT cut-offs generally demonstrated acceptable specificity when applied to our sample. However, the overall cognitive burden of the sample was limited relative to that observed in prior large-scale MS studies. CONCLUSION The current study provides initial data regarding the performance of select ePVTs among an MS sample. Results indicate most previously validated cut-offs avoid excessive false positive errors in a predominantly relapsing remitting MS sample. Further validation among MS patients with more advanced disease is warranted. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Purpose The pivotal role of microRNAs (miRNAs or miRs) has been proved in the pathogenesis of retinoblastoma. miR-224-3p is demonstrated to be involved in several tumors. However, the underlying mechanism of miR-224-3p in retinoblastoma is yet to be investigated. Therefore, this study was designed to identify the regulation of miR-224-3p in human retinoblastoma. Methods The expression pattern of miR-224-3p and large tumor suppressor 2 (LATS2) in retinoblastoma was measured by reverse transcription quantitative polymerase chain reaction. Afterward, the interaction between miR-224-3p and LATS2 was identified using a dual luciferase reporter gene assay. Next, gain-of-function and loss-of-function approaches were employed to examine the effects of miR-224-3p and LATS2 as well as their interaction on cell apoptosis, proliferation and angiogenesis abilities, and tumorigenesis. Whether the Hippo-YAP signaling pathway was involved in tumorigenesis was analyzed by determining downstream genes. Results LATS2 was downregulated in retinoblastoma, and its overexpression promoted apoptosis and suppressed proliferation of retinoblastoma cells. miR-224-3p, highly expressed in retinoblastoma, inhibited the expression of its target gene LATS2, which inhibited activation of the Hippo-YAP signaling pathway. Suppression of miR-224-3p promoted apoptosis while suppressing the proliferation of retinoblastoma cells and angiogenesis. Tumor progression induced by upregulation of miR-224-3p was diminished by restoration of LATS2. It was observed that tumor growth and angiogenesis were reduced by depleted miR-224-3p in the animal experiments. Conclusions The present study suggests that miR-224-3p targets LATS2 and blocks the Hippo-YAP signaling pathway activation, thus preventing the progression of retinoblastoma, which could be a new therapeutic target for retinoblastoma.Purpose Photoactivated cornea collagen cross-linking (CXL) increases corneal stiffness by initiating formation of covalent bonds between stromal proteins. Because CXL depends on diffusion to distribute the photoinitiator, a gradient of CXL efficiency with depth is expected that may affect the degree of stromal collagen organization. We used second harmonic generation (SHG) microscopy to investigate the differences in stromal collagen organization in rabbit eyes after corneal CXL in vivo as a function of depth and time after surgery. Methods Rabbit corneas were treated in vivo with either riboflavin/UV radiation (UVX) or Rose Bengal/green light (RGX) and evaluated 1 and 2 months after CXL. Collagen fibers were imaged with a custom-built SHG scanning microscope through the central cornea (350 µm depth, 225 × 225 µm en face images). The order coefficient (OC), a metric for collagen organization, and total SHG signal were computed for each depth and compared between treatments. Results OC values of CXL-treated corneas were larger than untreated corneas by 27% and 20% after 1 month and 38% and 33% after 2 months for the RGX and UVX, respectively.