siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.

Genetic manipulation of animal models is a fundamental research tool in biology and medicine but is challenging in large animals. In rodents, models can be readily developed by knocking out genes in embryonic stem cells or by knocking down genes through in vivo delivery of nucleic acids. Swine are a preferred animal model for studying the cardiovascular and immune systems, but there are limited strategies for genetic manipulation. Lipid nanoparticles (LNPs) efficiently deliver small interfering RNA (siRNA) to knock down circulating proteins, but swine are sensitive to LNP-induced complement activation-related pseudoallergy (CARPA). We hypothesized that appropriately administering optimized siRNA-LNPs could knock down circulating levels of plasminogen, a blood protein synthesized in the liver. siRNA-LNPs against plasminogen (siPLG) reduced plasma plasminogen protein and hepatic plasminogen mRNA levels to below 5% of baseline values. Functional assays showed that reducing plasminogen levels modulated systemic blood coagulation. Clinical signs of CARPA were not observed, and occasional mild and transient hepatotoxicity was present in siPLG-treated animals at 5 h post-infusion, which returned to baseline by 7 days. These findings advance siRNA-LNPs in swine models, enabling genetic engineering of blood and hepatic proteins, which can likely expand to proteins in other tissues in the future.

Trends in Authorship of Original Scientific Articles in Journal of Glaucoma: An Analysis of 25 Years Since the Initiation of the Journal.

PRéCIS:: Publications in glaucoma have seen an increase in the number of authors and disclosures per article, authors with dual degrees, and international authors, but contributions of women to articles published remains low. PURPOSE: Authorship trends have been studied across many medical specialties and in ophthalmology as a whole, but not specifically in glaucoma. The authors explored the authorship trends of original scientific articles in the Journal of Glaucoma. MATERIALS AND METHODS: The authors recorded the number of authors and disclosures per article, degree type of first and last authors, geographical origin of the corresponding author, and sex of first and last authors of original content from the Journal of Glaucoma published in 1992, 1997, 2002, 2007, 2012, and 2017. RESULTS: A total of 642 articles were analyzed. From 1992 to 2017, annual published articles increased from 38 to 242 (P=0.02), the mean number of authors per article increased from 3.2 to 5.2 (P<0.01), the mean number of disclosures per article increased from 0.3 to 1.0 (P=0.04), the proportion of first and last authors with dual degrees (medical plus advanced degrees) also increased (both P<0.03), whereas the proportion with a sole medical degree decreased (both P<0.05). There was a proportional decrease in articles from North America (P=0.03), and proportional increase from the "Far East" (P=0.04) and "Other" regions (P=0.04). No significant changes in proportions of female first and last authors were found (both P>0.28). CONCLUSIONS: Consistent with authorship trends across various other medical specialties, glaucoma has seen an increase in the number of authors and disclosures per article, authors with dual degrees, and authors from the "Far East" and "Other" regions. However, contributions of women to articles published in Journal of Glaucoma remain low.

Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes.

BACKGROUND: Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes. METHODS: This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia. RESULTS: A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001). CONCLUSIONS: GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.

To spray or not to spray? Understanding participation in an indoor residual spray campaign in Arequipa, Peru.

Current low participation rates in vector control programmes in Arequipa, Peru complicate the control of Chagas disease. Using focus groups (n = 17 participants) and semi-structured interviews (n = 71) conducted in March and May 2013, respectively, we examined barriers to and motivators of household participation in an indoor residual spray (IRS) campaign that had taken place one year prior in Arequipa. The most common reported barriers to participation were inconvenient spray times due to work obligations, not considering the campaign to be necessary, concerns about secondary health impacts (e.g. allergic reactions to insecticides), and difficulties preparing the home for spraying (e.g. moving heavy furniture). There was also a low perception of risk for contracting Chagas disease that might affect participation. The main motivator to participate was to ensure personal health and well-being. Future IRS campaigns should incorporate more flexible hours, including weekends; provide appropriate educational messages to counter concerns about secondary health effects; incorporate peer educators to increase perceived risk to Chagas in community; obtain support from community members and leaders to build community trust and support for the campaign; and assist individuals in preparing their homes. Enhancing community trust in both the need for the campaign and its operations is key.