Report of a self-resolving corneal viral papilloma in a dog.

A 10-month-old male castrated beagle dog, without prior history of ocular disease, was referred for a corneal mass of the right eye. A non-painful raised mass with frond-like projections originated from the dorsotemporal paraxial cornea of the right eye. In addition, a plaque-like conjunctival lesion and several raised, smooth masses of the eyelid were noted around the right eye. An incisional biopsy of the corneal mass and an excisional biopsy of the conjunctival mass were performed. Histopathology confirmed the clinical diagnosis of viral papilloma. Conservative management with monitoring was elected, and the lesion self-resolved 3 mo after initial appearance. Key clinical message: This case suggests that monitoring is appropriate for corneal lesions definitively diagnosed as viral papillomas, as they may be self-limiting.

Rapport d'un papillome viral cornéen auto-résolutif chez un chien. Un chien beagle mâle castré âgé de 10 mois, sans antécédent de maladie oculaire, a été envoyé pour consultation pour une masse cornéenne de l'oeil droit. Une masse surélevée non douloureuse avec des projections en forme de frondes provenait de la cornée paraxiale dorso-temporale de l'oeil droit. De plus, une lésion conjonctivale en forme de plaque et plusieurs masses surélevées et lisses de la paupière ont été notées autour de l'oeil droit. Une biopsie incisionnelle de la masse cornéenne et une biopsie excisionnelle de la masse conjonctivale ont été réalisées. L'histopathologie a confirmé le diagnostic clinique de papillome viral. Une prise en charge conservatrice avec surveillance a été choisie et la lésion s'est résolue d'elle-même 3 mois après l'apparition initiale.Message clinique clé :Ce cas suggère que la surveillance est appropriée pour les lésions cornéennes définitivement diagnostiquées comme des papillomes viraux, car elles peuvent être spontanément auto-limitantes.(Traduit par Dr Serge Messier).

Key stakeholders' views, experiences and expectations of patient and public involvement in healthcare professions' education: a qualitative study.

BACKGROUND: Patients and the public have an integral role in educating healthcare professionals. Authentic partnerships between higher education institutions and patients and the public are essential. This study examined key stakeholders' views, experiences and expectations of patient and public involvement (PPI) including the nature of the involvement and requirements for partnership. METHODS: Purposive and snowball sampling was used to recruit key stakeholders, including patients and members of the public involved in health professions education, and academics interested in PPI. Focus groups were held with patient and public participants, providing the opportunity to gain multiple perspectives in an interactive group setting. Academics with an interest in PPI were interviewed using a semi-structured approach. Topic guides were derived from the literature and piloted prior to data collection. Focus groups and interviews were conducted until data saturation was achieved. All data was audio-recorded, transcribed, anonymised and thematically analysed. RESULTS: Four focus groups were conducted involving 23 patient and public participants (median number of participants per focus group of 6). Nine interviews were conducted with academics (face-to-face [n = 8] or by telephone [n = 1]). Five themes were developed: previous experiences of PPI, training requirements, challenges/barriers to PPI, facilitators of PPI and future ideas for PPI. All participants held positive views of the value of PPI. Participants had mixed views in terms of training, which depended on the level of involvement, but similar views on the challenges and facilitators for PPI in education. There was agreement that PPI requires institutional vision and investment to build strong relationships and a culture of PPI best practice. CONCLUSIONS: There is a need for more strategic and formal involvement of patients and the public to ensure that that PPI becomes sustainably embedded in health professions education.

Optimizing corneal riboflavin administration in ex vivo horse, dog, rabbit, and pig samples for use in corneal collagen cross-linking.

PURPOSE: Determine optimal iontophoresis times for riboflavin delivery to the corneal stroma across different species and compare these to corneal injection. METHODS: Ex vivo horse, dog, rabbit, and pig globes were treated with riboflavin administered with either iontophoresis for 2.5-20 minutes with or without corneal epithelium; or with purpose-designed precise corneal injection (PCI) application with intact epithelium. Immediately following riboflavin administration, samples were harvested, frozen, and sectioned. Riboflavin penetration was imaged using fluorescence microscopy. RESULTS: Horse samples processed with iontophoresis without epithelium for 2.5, 5, and 7.5 minutes, and processed with intact epithelium for 20 minutes, had mean percent stromal penetration (%SPmean ) of 63.4%, 93.8%, 100.0%, and 0.0% (respectively). Dog samples processed with iontophoresis without epithelium for 2.5 and 5 minutes, had %SPmean of 60.7% and 82.1% (respectively). Pig samples processed with iontophoresis for 5 minutes without and with epithelium had %SPmean of 63.3% and 35.1% (respectively). Rabbit samples processed with iontophoresis without epithelium for 2.5 and 5 minutes, had %SPmean of 81.8% and 100.0% (respectively). For all injected volumes, riboflavin was observed spanning throughout the corneal stroma, and lamellar separation was noted surrounding all sites of injection. CONCLUSIONS: Both iontophoresis and injection via PCI needles provide efficient and effective means of riboflavin administration in ex vivo horse, dog, rabbit, and pig corneas. Epithelial debridement is required for stromal delivery of riboflavin using iontophoresis in horses. Following epithelial removal, riboflavin penetrated through the horse corneal stroma faster than all other species tested.

Development of a Sustained Release Nano-In-Gel Delivery System for the Chemotactic and Angiogenic Growth Factor Stromal-Derived Factor 1α.

Stromal-Derived Factor 1α (SDF) is an angiogenic, chemotactic protein with significant potential for applications in a range of clinical areas, including wound healing, myocardial infarction and orthopaedic regenerative approaches. The 26-min in vivo half-life of SDF, however, has limited its clinical translation to date. In this study, we investigate the use of star-shaped or linear poly(glutamic acid) (PGA) polypeptides to produce PGA-SDF nanoparticles, which can be incorporated into a tyramine-modified hyaluronic acid hydrogel (HA-TA) to facilitate sustained localised delivery of SDF. The physicochemical properties and biocompatibility of the PGA-SDF nanoparticle formulations were extensively characterised prior to incorporation into a HA-TA hydrogel. The biological activity of the SDF released from the nano-in-gel system was determined on Matrigel®, scratch and Transwell® migration assays. Both star-shaped and linear PGA facilitated SDF nanoparticle formation with particle sizes from 255-305 nm and almost complete SDF complexation. Star-PGA-SDF demonstrated superior biocompatibility and was incorporated into a HA-TA gel, which facilitated sustained SDF release for up to 35 days in vitro. Released SDF significantly improved gap closure on a scratch assay, produced a 2.8-fold increase in HUVEC Transwell® migration and a 1.5-fold increase in total tubule length on a Matrigel® assay at 12 h compared to untreated cells. Overall, we present a novel platform system for the sustained delivery of bioactive SDF from a nano-in-gel system which could be adapted for a range of biomedical applications.

A Fixed-Depth Microneedle Enhances Reproducibility and Safety for Corneal Gene Therapy.

PURPOSE: Drug delivery directly to the corneal stroma currently relies on microscopic injections that demonstrate low reproducibility and clinician-dependent variability. With use of biological drugs such as adeno-associated viral (AAV) vectors, precise and consistent drug deposition is critical to reduce concerns related to off-target transduction and the host's immune response to the viral capsid and/or transgene-derived product. Therefore, a precise corneal injection (PCI) microneedle was designed to allow accurate depth-specific injections into the corneal stroma in a macroscopic setting. METHODS: High-frequency ultrasound and confocal microscopy demonstrated the consistent ability to predetermine the precise injection depth using PCI needles of varying sizes. Next, a comparison between a standard 31-G needle and PCI needles was performed in vivo using AAV vector gene delivery. RESULTS: Intrastromal corneal injections using the PCI microneedle resulted in less vector leakage at the site of injection and fewer anterior chamber penetrations compared with a standard 31-G needle. Although reporter gene expression appeared similar when the vector was administered with either needle type, a trend toward increased vector genomes was noted in the PCI-injected corneas at the experimental conclusion. As hypothesized, corneal perforation resulted in increased detection of AAV vector genomes in nontarget tissues, highlighting the importance of consistency for biological drug applications in the cornea. CONCLUSIONS: Further development of the PCI microneedle is warranted especially for AAV corneal gene therapy and offers the potential to enhance transduction while significantly reducing safety concerns and intraclinician and interclinician injection variability.

AAV-mediated expression of HLA-G1/5 reduces severity of experimental autoimmune uveitis.

Non-infectious uveitis (NIU) is an intractable, recurrent, and painful disease that is a common cause of vision loss. Available treatments of NIU, such as the use of topical corticosteroids, are non-specific and have serious side effects which limits them to short-term use; however, NIU requires long-term treatment to prevent vision loss. Therefore, a single dose therapeutic that mediates long-term immunosuppression with minimal side effects is desirable. In order to develop an effective long-term therapy for NIU, an adeno-associated virus (AAV) gene therapy approach was used to exploit a natural immune tolerance mechanism induced by the human leukocyte antigen G (HLA-G). To mimic the prevention of NIU, naïve Lewis rats received a single intravitreal injection of AAV particles harboring codon-optimized cDNAs encoding HLA-G1 and HLA-G5 isoforms one week prior to the induction of experimental autoimmune uveitis (EAU). AAV-mediated expression of the HLA-G-1 and -5 transgenes in the targeted ocular tissues following a single intravitreal injection of AAV-HLA-G1/5 significantly decreased clinical and histopathological inflammation scores compared to untreated EAU eyes (p < 0.04). Thus, localized ocular gene delivery of AAV-HLA-G1/5 may reduce the off-target risks and establish a long-term immunosuppressive effect that would serve as an effective and novel therapeutic strategy for NIU, with the potential for applications to additional ocular immune-mediated diseases.

Multi-locus DNA sequence analysis, antifungal agent susceptibility, and fungal keratitis outcome in horses from Southeastern United States.

Morphological characterization and multi-locus DNA sequence analysis of fungal isolates obtained from 32 clinical cases of equine fungal keratitis (FK) was performed to identify species and determine associations with antifungal susceptibility, response to therapy and clinical outcome. Two species of Aspergillus (A. flavus and A. fumigatus) and three species of Fusarium (F. falciforme, F. keratoplasticum, and F. proliferatum) were the most common fungi isolated and identified from FK horses. Most (91%) equine FK Fusarium nested within the Fusarium solani species complex (FSSC) with nine genetically diverse strains/lineages, while 83% of equine FK Aspergillus nested within the A. flavus clade with three genetically diverse lineages. Fungal species and evolutionary lineage were not associated with clinical outcome. However, species of equine FK Fusarium were more likely (p = 0.045) to be associated with stromal keratitis. Species of Aspergillus were more susceptible to voriconazole and terbinafine than species of Fusarium, while species of Fusarium were more susceptible to thiabendazole than species of Aspergillus. At the species level, A. fumigatus and A. flavus were more susceptible to voriconazole and terbinafine than F. falciforme. Natamycin susceptibility was higher for F. falciforme and A. fumigatus compared to A. flavus. Furthermore, F. falciforme was more susceptible to thiabendazole than A. flavus and A. fumigatus. These observed associations of antifungal sensitivity to natamycin, terbinafine, and thiabendazole demonstrate the importance of fungal identification to the species rather than genus level. The results of this study suggest that treatment of equine FK with antifungal agents requires accurate fungal species identification.

The enduring effects of psychodynamic treatments vis-à-vis alternative treatments: A multilevel longitudinal meta-analysis.

Although evidence suggests that the benefits of psychodynamic treatments are sustained over time, presently it is unclear whether these sustained benefits are superior to non-psychodynamic treatments. Additionally, the extant literature comparing the sustained benefits of psychodynamic treatments compared to alternative treatments is limited with methodological shortcomings. The purpose of the current study was to conduct a rigorous test of the growth of the benefits of psychodynamic treatments relative to alternative treatments across distinct domains of change (i.e., all outcome measures, targeted outcome measures, non-targeted outcome measures, and personality outcome measures). To do so, the study employed strict inclusion criteria to identify randomized clinical trials that directly compared at least one bona fide psychodynamic treatment and one bona fide non-psychodynamic treatment. Hierarchical linear modeling (Raudenbush, Bryk, Cheong, Congdon, & du Toit, 2011) was used to longitudinally model the impact of psychodynamic treatments compared to non-psychodynamic treatments at post-treatment and to compare the growth (i.e., slope) of effects beyond treatment completion. Findings from the present meta-analysis indicated that psychodynamic treatments and non-psychodynamic treatments were equally efficacious at post-treatment and at follow-up for combined outcomes (k=20), targeted outcomes (k=19), non-targeted outcomes (k=17), and personality outcomes (k=6). Clinical implications, directions for future research, and limitations are discussed.