SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.

BackgroundWe aimed to synthesize the evidence of a causal effect and draw inferences about whether Canadian primary care reforms improved health system performance based on measures of health service utilization, processes of care, and physician productivity.MethodsWe searched the Embase, PubMed and Web of Science databases for records from 2000 to September 2015. We based our risk of bias assessment on the Grading of Recommendations Assessment, Development and Evaluation guidelines. Full-text studies were synthesized and organized according to the three outcome categories: health service utilization, processes of care, and physician costs and productivity.ResultsWe found moderate quality evidence that team-based models of care led to reductions in emergency department use, but the evidence was mixed for hospital admissions. We also found low quality evidence that team-based models, blended capitation models and pay-for-performance incentives led to small and sometimes non-significant improvements in processes of care. Studies examining new payment models on physician costs and productivity were of high methodological quality and provided a coherent body of evidence assessing enhanced fee-for-service and blended capitation payment models.ConclusionA small number of studies suggested that team-based models contributed to reductions in emergency department use in Quebec and Alberta. Regarding processes of diabetes care, studies found higher rates of testing for blood glucose levels, retinopathy and cholesterol in Alberta’s team-based primary care model and in practices eligible for pay-for-performance incentives in Ontario. However pay-for-performance in Ontario was found to have null to moderate effects on other prevention and screening activities. Although blended capitation payment in Ontario contributed to decreases in the number of services delivered and patients seen per day, the number of enrolled patients and number of days worked in a year was similar to that of enhanced fee-for-service practices.

Dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) commonly are presented with concurrent clinical, physical, and historical findings consistent with hyperadreno-corticism (HAC) at the time of vision loss. Thirteen dogs diagnosed with SARDS on the basis of complete ophthalmic examination and extinguished bright-flash electroretinogram were evaluated for steroid hormonal abnormalities. Signalment, case history, physical examination, and clinicopathological findings were recorded. Serum cortisol and sex-hormone concentrations were measured before and after adrenocorticotropic hormone (ACTH) stimulation. Clinical signs of HAC, systemic hypertension, and proteinuria were commonly found in dogs with SARDS. Elevations in one or more sex hormones were found in 11 (85%) of 13 dogs (95% confidence interval [CI] 65% to 100%); cortisol was elevated in nine (69%) of 13 dogs (95% CI 44% to 94%). A minority of dogs (three [23%] of 13; 95% CI 0.2% to 46%) exhibited only an increase in adrenal sex hormones. Only one dog had completely normal ACTH stimulation test results. Symptoms of HAC were associated with abnormal ACTH stimulation results. Routine ACTH stimulation testing to evaluate cortisol and sex hormones, blood pressure screening, and urinalysis are recommended in these animals.

The results of our study identified a population of ERU cases with an active intraocular Leptospira infectious process in the Southern United States. The diagnosis of intraocular leptospirosis required ocular fluid sampling for PCR or culture. Twenty-one percent of ocular fluid samples were positive by culture and forty-five percent by PCR; no control horses were positive by either culture or PCR. These findings are in contrast to a recent study from the Southeastern US that showed no evidence of bacterial DNA by PCR and supports the conclusion that a regional variation in Leptospira infections exists. The most common culture isolate was the serovar pomona; additionally, we report the first cases of serovar grippotyphosa outside of Europe. Title Role of intraocular Leptospira infections in the pathogenesis of Equine Recurrent Uveitis in the Southern United States.Abstract: Equine Recurrent Uveitis (ERU) has been linked to leptospirosis in Europe, however regional differences exist in reports from the United States. The objective of this study was to investigate the role of intraocular leptospiral infections in horses with ERU in the Southern United States. Blood and ocular fluid samples were collected from horses with ERU as well as normal controls. Leptospira serology was performed using microscopic agglutination test (MAT). Aqueous and vitreous humor samples were obtained and submitted for aerobic and Leptospira culture, PCR and MAT. Twenty-one control horses (40 eyes) and 31 ERU horses (46 eyes) were available. Serology was available for 48/52 horses: 16/21 control and 23/27 affected horses were positive for at least one serovar; bratislava was the most common serovar identified. Bacillus sp. and Micrococcus sp. were cultured from one control eye; Streptococcus sp. (n=1) and Leptospira (n=6) from the eyes of 6 ERU horses. Leptospira isolates belonged to serogroup pomona (n=4) and grippotyphosa (n=2). PCR results were positive in 14/31 (45%) horses with ERU; no control horses were positive by PCR (p=0.0001). MAT was positive for 17/24 of ERU horses (71%) and 1/21 (4.7%) of normal horses (p<0.0001). Horses with ERU had a high prevalence of Leptospira infection based on PCR and MAT results from intraocular fluids compared to controls. The diagnosis of intraocular infections was not aided by serology and required specific, invasive sampling of ocular fluid. Leptospira infection should be considered as a cause of ERU in the Southern United States.

Keratomycosis is rarely reported in dogs. The purpose of this study was to review the signalment, clinical characteristics, predisposing factors, and outcome of 11 cases of canine keratomycosis. Medical records of included dogs were reviewed and follow-up information was obtained by re-examination of patients following their initial diagnosis. All 11 patients possessed predisposing factors for fungal keratitis, including an underlying endocrinopathy, pre-existing corneal disease, intraocular surgery, and/or prolonged use of either topical antibiotics or corticosteroids at the time of initial examination. Diagnostic techniques included corneal cytology demonstrating yeast or hyphae in 6 of 11 eyes, and fungal cultures with positive results in 7 of 11 eyes. Fungal organisms isolated included Cladosporium spp. (n = 1), Chrysosporium spp. (n = 1), Curvularia spp. (n = 2), Aspergillus spp. (n = 1), Penicillium spp. (n = 1), and Phialemonium spp. (n = 1). Of the 11 patients, 6 responded to medical management alone. Two resolved after a superficial keratectomy, and three were enucleated due to either endophthalmitis or progression of corneal disease. This study identified potential risk factors for developing fungal keratitis.

In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

Integrins are cell adhesion molecules important in cell-cell and cell-extracellular matrix interactions. These interactions are vital to numerous physiological processes including corneal wound healing. This review discusses the structure of integrins as well as the various roles that integrins play in the corneal wound healing process. Integrin profile abnormalities identified in various corneal pathological conditions are also reviewed.

Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with lethal human clinical strain HSV-1(McKrae). VC2 vaccination in mice produced superior protection and morbidity control in comparison to its parental strain HSV-1(F). Specifically, after HSV-1(McKrae) ocular challenge, all VC2 vaccinated-mice survived, while 30% of the HSV-1(F)-vaccinated and 100% of the mock-vaccinated mice died post challenge. VC2-vaccinated mice did not exhibit any symptoms of ocular infection and completely recovered from initial conjunctivitis. In contrast, HSV-1(F)-vaccinated mice developed time-dependent progressive keratitis characterized by corneal opacification, while mockvaccinated animals exhibited more severe stromal keratitis characterized by immune cell infiltration and neovascularization in corneal stroma with corneal opacification. Cornea in VC2immunized mice exhibited significantly increased infiltration of CD3 + T lymphocytes and decreased infiltration of Iba1+ macrophages in comparison to mock-or HSV-1(F)-vaccinated groups. VC2 immunization produced higher virus neutralization titers than HSV-1(F) post challenge. Furthermore, VC-vaccination significantly increased the CD4 T central memory (TCM) subsets and CD8 T effector memory (TEM) subsets in the draining lymph nodes following ocular HSV-1 (McKrae) challenge, then mock-or HSV-1(F)-vaccination. These results indicate that VC2 vaccination produces a protective immune response at the site of challenge to protect against HSV-1-induced ocular pathogenesis.