A review and update on orphan drugs for the treatment of noninfectious uveitis

Introduction: Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation. Area covered The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA). Our perspective IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease

A heterozygous moth genome provides insights into herbivory and detoxification

How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al

Bilateral papillitis and vitritis as the initial ophthalmologic finding in a patient with complex medical history, leading to diagnosis of multisystem sarcoidosis

Aim: To report a case of bilateral papillitis as the initial ophthalmologic presentation in a patient with complex medical history and multisystemic symptoms, eventually revealing a diagnosis of sarcoidosis. Methods: Retrospective interventional case report. Report: A 54-year-old Caucasian woman presented with bilateral decreased vision, photophobia and eye pain for a month. She was referred for evaluation of disc edema with questionable history of vitritis. She had a complicated medical history and systemic symptoms, including: multiple tick bites; focal neurologic symptoms including tingling, headache, numbness of fingers, and stiff neck; systemic immune disease with thyroid nodule; and chest strain, mild shortness of breath, and palpitations, leading to a large differential diagnosis. Further workup ruled out infectious diseases and multiple sclerosis. After chest imaging, she was finally diagnosed via biopsy with sarcoidosis. Therapy included combined high dose prednisone taper and ongoing methotrexate. Both ocular and systemic symptoms improved after treatment, but there was limited improvement of scotoma in the left eye. Conclusion: This report provides a case for ophthalmologists for papillitis as the initial manifestation of sarcoidosis, but with various potential differential diagnoses during work up. : This case highlights a 54-year-old woman with papillitis who presented with a complicated history and wide variety of systemic symptoms, creating a large differential diagnosis and challenging work up, ultimately resulting in a diagnosis of sarcoidosis via biopsy. The authors feel that papillitis is an underappreciated feature of ocular sarcoid. Keywords: Papillitis, Sarcoidosis, Differential diagnosi

Spatial-Temporal Differences in the Effect of Epidemic Risk Perception on Potential Travel Intention: A Macropsychology-Based Risk Perception Perspective

Most of the previous studies on the impact of risk perception on travel intention are based on an individual psychological perspective, and the understanding based on the perspective of macropsychology is insufficient. Analyzing the temporal and spatial characteristics of risk perception theory at the macropsychological and regional levels will expand the scope of risk perception theory, which may help to promote the orderly recovery of tourism activities under the normalization of epidemics at the regional level. This study uses Baidu big data, through a panel VAR analysis, to explore the impact of people’s epidemic risk perception on travelers intentions from a macropsychological level and to analyze the temporal and spatial differences of this impact. From a temporal perspective, this study found that the early stage of epidemic risk perception had a negative impact on travel intentions, and later, a compensatory effect on travelers intentions appeared. From the perspective of risks at different threat levels, the Wuhan epidemic with a high degree of threat had a greater impact, while foreign epidemics had less impact. From the perspective of spatial differences, this study indicated that the negative impact of attention to epidemics on attention to tourism basically shows a gradual decay from the core to secondary and then to peripheral areas. This research will reveal some new findings on the impact of perceived risk on behavior intention at the temporal and spatial levels, and will have certain reference value for regional tourism restoration and marketing under the influence of epidemics

Vitreous and plasma VEGF levels as predictive factors in the progression of proliferative diabetic retinopathy after vitrectomy.

To investigate the vitreous and plasma levels of vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to determine whether they predict a disease prognosis after primary vitrectomy.Fifty patients (50 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 56 healthy controls (56 eyes) were enrolled in this retrospective study. Clinical data were collected and analyzed. Vitreous and plasma VEGF concentrations were measured using enzyme-linked immunosorbent assays. VEGF levels and clinical data were compared and analyzed to see if they provide a prognosis of PDR progression after primary vitrectomy at more than 6 months follow-up. Correlation of VEGF concentrations between vitreous fluid and plasma was analyzed.The average BCVA was significantly improved after surgery (P<0.001). Vitreous and plasma VEGF levels were significantly elevated in PDR patients than those in healthy controls (P vitreous<0.001; P plasma<0.001). Both vitreous and plasma VEGF levels were significantly higher in PDR progression group than in stable group (P vitreous < 0.001; P plasma = 0.004). Multivariate logistic regression analyses showed that the increased vitreous VEGF level was associated with the progression of PDR after primary PPV (OR = 1.539; P = 0.036). Vitreous VEGF level was positively associated with plasma VEGF level in PDR patients (P<0.001).The increased VEGF level in vitreous fluid may be identified as a significant predictive factor for the outcome of vitrectomy in patients with PDR

Effects of Stocking Density on Fatty Acid Metabolism by Skeletal Muscle in Mice

Specific pathogen-free (SPF) grade laboratory animals are kept in specific cages for life. The limited space could affect the characterization of colonization and dynamic changes related to gut microorganisms, and affect adipokines, even further affecting the fat synthesis and muscle quality of animals. The objective of this study was to analyze the stocking density on the dynamic distribution of gut microbiota, fat synthesis and muscle quality of SPF grade Kunming mice. Three housing densities were accomplished by raising different mice per cage with the same floor size. Kunming mice were reared at low stocking density (LSD, three mice a group), medium stocking density (MSD, 5 mice a group), and high stocking density (HSD, 10 mice a group) for 12 weeks. The results demonstrated that the stocking density affected intestinal microbial flora composition. We found that compared with the MSD group, the abundance of Lactobacillus in the LSD group and the HSD group decreased, but the abundance of unclassified_Porphyromonadaceae increased. Moreover, fat synthesis and muscle quality were linked to the intestinal microbial flora and stocking density. Compared with the LSD group and the HSD group, the MSD group had a more balanced gut flora, higher fat synthesis and higher muscle quality. Overall, this study demonstrated that stocking density could affect gut microbiota composition, and reasonable stocking density could improve fat synthesis and muscle quality. Our study will provide theoretical support for the suitable stocking density of laboratory animals