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Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P

Re-epithelialization of wounds is a critical element of wound closure. Growth factors have been used in combination with conventional wound management to promote closure, but the method of delivery has been limited to the topical application of ointment formulations. Cytoactive factors delivered in this way have short resident times in wounds and have met with limited success. Here, we demonstrate that methods used to covalently immobilize proteins on synthetic materials can be extended to immobilize cytoactive factors such as the epidermal growth factor (EGF) onto the wound beds of genetically diabetic mice that exhibit impaired healing. Full-thickness splinted excisional wounds were created in diabetic (db/db) mice with a well-defined silicone splint to limit wound contracture. Wound surfaces were treated with a reducing agent to expose sulfhydryl groups and subsequently treated with EGF modified with a heterobifunctional crosslinker. This allowed for the covalent immobilization of the EGF to the wound surface. The conjugation chemistry was validated in vitro and in vivo. In a separate group of mice, wounds were topically treated twice daily with soluble EGF. The mice were evaluated over 11 days for wound closure. This covalent immobilization strategy resulted in EGF being retained on the wound surface for 2 days and significantly increased epithelial wound closure by 20% compared to wounds treated with topical EGF or topical vehicle. Covalent immobilization was not only therapeutically effective but also delivered a markedly reduced load of growth factor to the wound surface compared to topical application (when only 180 ng of EGF was immobilized onto the wound surface in comparison with 7200 ng of topically applied EGF over a period of 11 days). No adverse effects were observed in treated wounds. Results obtained provide proof of concept for the effectiveness of covalent immobilization in the treatment of dysregulated wounds. The covalent immobilization of cytoactive factors represents a potentially transformative approach to the management of difficult chronic wounds.

The selection of oxide materials for catalyzing the oxygen evolution reaction in acid-based electrolyzers must be guided by the proper balance between activity, stability and conductivity-a challenging mission of great importance for delivering affordable and environmentally friendly hydrogen. Here we report that the highly conductive nanoporous architecture of an iridium oxide shell on a metallic iridium core, formed through the fast dealloying of osmium from an Ir25Os75 alloy, exhibits an exceptional balance between oxygen evolution activity and stability as quantified by the activity-stability factor. On the basis of this metric, the nanoporous Ir/IrO2 morphology of dealloyed Ir25Os75 shows a factor of ~30 improvement in activity-stability factor relative to conventional iridium-based oxide materials, and an ~8 times improvement over dealloyed Ir25Os75 nanoparticles due to optimized stability and conductivity, respectively. We propose that the activity-stability factor is a key "metric" for determining the technological relevance of oxide-based anodic water electrolyzer catalysts.

ObjectiveTo evaluate repeatability and reproducibility of tear osmolarity measured using the TearLab™ osmometer in normal dogs and to assess its diagnostic potential in dogs with keratoconjunctivitis sicca (KCS).Animals studiedBeagle dogs; six normal and five with KCS.ProceduresTear osmolarity and Schirmer tear test-1 (STT-1) values were obtained at various times. Normal dogs were assessed for diurnal variation and repeatability and reproducibility of measurements. Dogs with KCS were evaluated before and after 5 months' topical twice-daily therapy with 2% cyclosporine.ResultsMean ± SD tear osmolarity (mOsm/L) was significantly higher in normal dogs (337.4 ± 16.2) than in dogs with KCS before therapy (306.2 ± 18.0; P < 0.0001), but not following therapy with 2% cyclosporine (330.5 ± 13.7; P = 1.00). Osmolarity readings lower than 325.5 mOsm/L were suggestive of KCS (84.8% sensitivity and 87.1% specificity). In normal dogs, tear osmolarity readings were stable during the daytime (P = 0.99). Repeated measurements revealed high variability and typically poor-to-moderate repeatability and reproducibility, although this was improved by taking three successive measurements at each session. Considering combined data from all dogs, a positive correlation existed between STT-1 and tear osmolarity measurements (Pearson's correlation test, P = 0.04, r = 0.62).ConclusionsCanine tear osmolarity as determined by TearLab™ osmometer was variable, required multiple readings to be informative, and differed from values reported for humans. Dogs with KCS had a lower tear osmolarity than did normal dogs, and this increased following cyclosporine therapy.

Objective Animals Studied Procedure Results Conclusions The aim of this report was to provide a clinical description and clinical, ultrasonographic, and histologic images of a foal with microphthalmia and multiple ocular abnormalities.A 12‐h old Friesian‐American Paint Horse crossbred filly presented for blindness, microphthalmia and marked ventral strabismus in both eyes.A complete ophthalmic examination was performed. Ultrasound biomicroscopy and B‐mode ultrasonography were performed. The globes were submitted for histopathology.Ultrasound biomicroscopy demonstrated a hyperechoic cornea void of the typical epithelium, stroma, and Descemet's membrane layers. The anterior chamber was spanned by thick strands of hyperechoic tissue extending from the iris to the cornea. The lens was not visualized. B‐mode ultrasound showed aphakia and mild, mottled echogenicity within the vitreous with no evidence of retinal detachment. On histopathology, both globes were microphthalmic with poorly defined corneal tissue. The anterior chambers were poorly formed and contained lacrimal glandular tissue. Portions of iridal tissue were present, but no lenses were noted. The retinas were segmentally detached and markedly atrophied with areas of retina dysplasia noted.This report provides a clinical, ultrasonographic and histologic description of a rare, congenital condition in a foal characterized by microphthalmia, aphakia, poorly defined corneal tissue, choristomatous differentiation of the anterior segment and retinal dysplasia. [ABSTRACT FROM AUTHOR]

PurposeTreatment with corticosteroids can result in ocular hypertension and may lead to the development of steroid-induced glaucoma. The extent to which biomechanical changes in trabecular meshwork (TM) cells and extracellular matrix (ECM) contribute toward this dysfunction is poorly understood.MethodsPrimary human TM (HTM) cells were cultured for either 3 days or 4 weeks in the presence or absence of dexamethasone (DEX), and cell mechanics, matrix mechanics and proteomics were determined, respectively. Adult rabbits were treated topically with either 0.1% DEX or vehicle over 3 weeks, and mechanics of the TM were determined.ResultsTreatment with DEX for 3 days resulted in a 2-fold increase in HTM cell stiffness, and this correlated with activation of extracellular signal-related kinase 1/2 (ERK1/2) and overexpression of α-smooth muscle actin (αSMA). Further, the matrix deposited by HTM cells chronically treated with DEX is approximately 4-fold stiffer, more organized, and has elevated expression of matrix proteins commonly implicated in glaucoma (decorin, myocilin, fibrillin, secreted frizzle-related protein [SFRP1], matrix-gla). Also, DEX treatment resulted in a 3.5-fold increase in stiffness of the rabbit TM.DiscussionThis integrated approach clearly demonstrates that DEX treatment increases TM cell stiffness concurrent with elevated αSMA expression and activation of the mitogen-activated protein kinase (MAPK) pathway, stiffens the ECM in vitro along with upregulation of Wnt antagonists and fibrotic markers embedded in a more organized matrix, and increases the stiffness of TM tissues in vivo. These results demonstrate glucocorticoid treatment can initiate the biophysical alteration associated with increased resistance to aqueous humor outflow and the resultant increase in IOP.

ObjectiveTo describe the lacrimal system of snakes using contrast micro-computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein passage ('Jones') testing, histology, and gross dissection.Animals studiedOne royal python and 19 snake cadavers representing 10 species.ProceduresDirect observation following injection of fluorescein into the subspectacular space, micro-CT following injection of three contrast agents into the subspectacular space, gross dissection following injection of latex into the subspectacular space, and histopathology.ResultsInjection of fluorescein confirmed patency, but not course of the lacrimal duct. Barium enabled clear visualization of the lacrimal duct, whereas two iodinated contrast agents proved inadequate. Collectively, micro-CT, anatomic dissections, and histology suggest tears are produced by a single, large, serous, retrobulbar gland, released into the subspectacular space via several ductules, and drained through a single punctum originating in the ventronasal subspectacular space, and the lacrimal duct, which takes one of three routes of variable tortuosity before opening into the oral cavity in close association with the opening of the duct of the vomeronasal organ.ConclusionsThe ophidian lacrimal duct has a generally tortuous course, and the details of its anatomy are species-variable. The tortuous course of the duct likely predisposes snakes to duct occlusion and must be considered when planning medical and surgical interventions in snakes with pseudobuphthalmos and subspectacular abscessation.

Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used.

Objectives: It has been suggested that psychosocial factors are related to survival time of inpatients with cancer. However, there are not many studies examining the relationship between spiritual well-being (SWB) and survival time among countries. This study investigated the relationship between SWB and survival time among three East Asian countries. Methods: This international multicenter cohort study is a secondary analysis involving newly admitted inpatients with advanced cancer in palliative care units in Japan, South Korea, and Taiwan. SWB was measured using the Integrated Palliative Outcome Scale (IPOS) at admission. We performed multivariate analysis using the Cox proportional hazards model to identify independent prognostic factors. Results: A total of 2,638 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. The median survival time was 18.0 days (95% confidence interval [CI] 16.5–19.5) in Japan, 23.0 days (95% CI 19.9–26.1) in Korea, and 15.0 days (95% CI 13.0–17.0) in Taiwan. SWB was a significant factor correlated with survival in Taiwan (hazard ratio [HR] 1.27; 95% CI 1.01–1.59; p = 0.04), while it was insignificant in Japan (HR 1.10; 95% CI 1.00–1.22; p = 0.06), and Korea (HR 1.02; 95% CI 0.77–1.35; p = 0.89). Significance of results: SWB on admission was associated with survival in patients with advanced cancer in Taiwan but not Japan or Korea. The findings suggest the possibility of a positive relationship between spiritual care and survival time in patients with far advanced cancer. [ABSTRACT FROM AUTHOR]

Objective: This case report describes the successful correction of partial obstruction of the NL duct in a cat by means of a modified retrograde NL duct cannulation using a steerable angle‐tipped hydrophilic guidewire (AH guidewire) following a paranasal incision. Animal Studied: A 2‐year‐old neutered male American domestic shorthair cat was referred to the Purdue University Veterinary Hospital (PUVH) for chronic epiphora suspected secondary to nasolacrimal (NL) system obstruction. Procedures: At the first visit, the cat had epiphora OD and facial dermatitis but no other abnormalities on physical and ophthalmic examinations. Computed tomography (CT)‐dacryocystorhinography revealed partial obstruction of the NL duct secondary to stenosis near the distal root of the right maxillary third premolar (107). A digital three‐dimensional (3D) model of the right maxilla and NL duct was created for inspection and virtual cannulation of the NL. The model was 3D printed and cannulation of the NL duct was rehearsed with various stent materials. Retrograde NL stenting with the guidance of a steerable angle‐tipped hydrophilic guidewire was conducted following a paranasal incision. A urethral catheter was cannulated over the guidewire and maintained for 44 days. Results: The epiphora resolved immediately after stenting. At 21 days post‐stenting, the cat developed acute bullous keratopathy secondary to self‐trauma which was treated with a third eyelid flap. On the final follow‐up communication with the owner at 210 days post‐stenting, no epiphora or any other concerns were reported. Conclusion: To the authors' knowledge, this is the first report of successful NL stenting and resolution of epiphora in a cat with a partial NL system obstruction. [ABSTRACT FROM AUTHOR]

Objective: Accurate prognostication is important for patients and their families to prepare for the end of life. Objective Prognostic Score (OPS) is an easy-to-use tool that does not require the clinicians' prediction of survival (CPS), whereas Palliative Prognostic Score (PaP) needs CPS. Thus, inexperienced clinicians may hesitate to use PaP. We aimed to evaluate the accuracy of OPS compared with PaP in inpatients in palliative care units (PCUs) in three East Asian countries.Method: This study was a secondary analysis of a cross-cultural, multicenter cohort study. We enrolled inpatients with far-advanced cancer in PCUs in Japan, Korea, and Taiwan from 2017 to 2018. We calculated the area under the receiver operating characteristics (AUROC) curve to compare the accuracy of OPS and PaP.Results: A total of 1,628 inpatients in 33 PCUs in Japan and Korea were analyzed. OPS and PaP were calculated in 71.7% of the Japanese patients and 80.0% of the Korean patients. In Taiwan, PaP was calculated for 81.6% of the patients. The AUROC for 3-week survival was 0.74 for OPS in Japan, 0.68 for OPS in Korea, 0.80 for PaP in Japan, and 0.73 for PaP in Korea. The AUROC for 30-day survival was 0.70 for OPS in Japan, 0.71 for OPS in Korea, 0.79 for PaP in Japan, and 0.74 for PaP in Korea.Significance Of Results: Both OPS and PaP showed good performance in Japan and Korea. Compared with PaP, OPS could be more useful for inexperienced physicians who hesitate to estimate CPS. [ABSTRACT FROM AUTHOR]