A Builder's Guide to Water and Energy

The work on which this report is based was supported in part by funds provided by the Office of Water Research and Technology (Project A-Q65-ALAS), US. Department of the interior, Washington, D.C., as authorized by the Water Research and Development Act of 1978

Choroidal microvascular repair after argon laser photocoagulation. Ultrastructural observations

Acute laser injury to the tapetum of the feline retina produces thrombosis of the choriocapillaris. Early changes are characterized by the appearance of platelet-fibrin thrombi within capillary loops and disruption of endothelial integrity. By 4 days, thrombi have disappeared, and the endothelium shows regenerative changes. No endothelial cell mitotic activity is seen. The endothelial cytoplasm becomes plump, and there is a loss of the fenestrations adjacent to Bruch's membrane. By 10-20 days, the capillary structure shows gradual restoration. At 30 days, endothelial cell fenestrae are clearly evident adjacent to Bruch's membrane. The reparative process in this model appears to evolve as a result of thrombolysis and endothelial cell activation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Congenital Ocular Toxoplasmosis

Congenital ocular toxoplasmosis is a significant cause of blindness. Retinochoroiditis is the most common finding, but other ocular manifestations include microphthalmus, nystagmus, strabismus, and ptosis. The serologic tests and lymphocyte stimulation test are the most useful aids in making the diagnosis. Pyrimethamine, sulfonamides, and corticosteroids are useful to treat active lesions. Primary care physicians, obstetricians, and ophthalmologists may help to prevent transmission of the disease and its serious ocular sequelae