Comparison of Lateral Flow to Other Pregnancy Determination Methods in Order to Determine Accuracy of Pregnancy Status in Beef Cattle Pre and Postpartum

Study Description: Blood samples were collected from six different Bos taurus herds between day 27 and 285 of gestation (heifers n = 1,205 and cows n = 1,539). Blood samples to determine PAG clearance interval were collected weekly postpartum for up to 12 weeks (heifers n = 418 and cows n = 657). Serum was tested using the lateral flow test and were read by two technicians who were blind to pregnancy status. Level of agreement between the tests were determined by Pearson’s correlation coefficients and Kappa scores. The MIXED procedure of SAS was used to evaluate the effect of dpp and age (heifers or cows) on postpartum test results. There was a positive correlation between transrectal ultrasonography and the lateral flow test (r2 = 0.71; P \u3c 0.01), and agreement between the two tests was very good (Kappa = 0.84). Of the animals that were diagnosed nonpregnant by transrectal ultrasonography, 5.61% were called pregnant by the lateral flow test. Of the animals diagnosed pregnant by transrectal ultrasonography, 2.00% were called not pregnant by the lateral flow test. Thus, a 92.38% agreement occurred between the two methods. For postpartum samples, there was no effect (P = 0.21) of age, but there was an effect of dpp (P \u3c 0.01) and a tendency for a dpp by age interaction (P = 0.06). All animals were still considered pregnant from the previous pregnancy through 35 dpp (100 ± 2.58%). The percentage of females receiving a false positive test result further decreased with time postpartum, by 77 dpp there were 13.72 ± 3.16% of the females positive for pregnancy and at 84 dpp there were 4.11 ± 4.39% positive for pregnancy detection

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

Pediatric emergency department discharge instructions for Spanish-speaking families

Objectives: Patients who speak Spanish are less likely to comply with discharge instructions, adhere to appointments, and take medications than English-speaking patients. However, adherence is improved when discharge instructions are provided in Spanish. This study was designed to assess the frequency of providing written discharge instructions in Spanish to patients who speak Spanish and request interpretation services, and to determine factors associated with receiving written discharge instructions in the preferred language in a pediatric emergency department (ED). Methods: This was a retrospective cross-sectional study of all discharges of Spanish-speaking patients who requested an interpreter in 1 year from a large urban pediatric ED and an associated community ED. Multivariable logistic regression was used to identify patient and visit level characteristics associated with receiving written discharge instructions in Spanish. Results: Sixty-one percent of 11,545 patient encounters where a Spanish interpreter was requested received written discharge instructions in Spanish. Patients aged 1 to 3 years (adjusted odds ratio [aOR], 2.87; 95% CI, 2.18–3.77) and aged 4 to 12 years (aOR, 2.06; 95% CI, 1.6–2.65), those seen without a trainee (aOR, 1.37; 95% CI, 1.25–1.5), and those with low acuity triage levels (aOR, 1.6; 95% CI, 1.29–1.97) were more likely to receive discharge instruction in Spanish. Female patients were less likely to receive Spanish discharge instructions (aOR, 0.9; 95% CI, 0.83–0.97). Conclusions: Discharged pediatric ED patients often do not receive written instructions in the preferred language. Patient and provider factors are associated with receiving written instructions in Spanish. Quality improvement efforts are needed to ensure appropriate language discharge education

Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.

BACKGROUND:Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure. METHODS:We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later with oxazolone or vehicle for ten consecutive days on the labia. We evaluated labiar sensitivity to touch, local mast cell accumulation, and hyperinnervation after ten challenges. RESULTS:Oxazolone-challenged mice developed significant tactile sensitivity that persisted for over three weeks after labiar allergen exposures ceased. Allergic sites were characterized by mast cell accumulation, sensory hyper-innervation and infiltration of regulatory CD4+CD25+FoxP3+ T cells as well as localized early increases in transcripts encoding Nerve Growth Factor and nerve-mast cell synapse marker Cell Adhesion Molecule 1. Local depletion of mast cells by intra-labiar administration of secretagogue compound 48/80 led to a reduction in both nerve density and tactile sensitivity. CONCLUSIONS:Mast cells regulate allergy-provoked persistent sensitivity to touch. Mast cell-targeted therapeutic strategies may provide novel means to manage and limit chronic pain conditions associated with atopic disease