Idiopathic Canine Laryngeal Paralysis as One Sign of a Diffuse Polyneuropathy: An Observational Study of 90 Cases (2007-2013).

OBJECTIVE: To determine survival and incidence of complications in dogs with idiopathic laryngeal paralysis (ILP) and concurrent neurologic signs. STUDY DESIGN: Observational study. ANIMALS: Dogs (n = 90) with ILP. METHODS: Medical records (January 2007-June 2013) of dogs with ILP were reviewed. Neurologic comorbidities, including pelvic limb neurologic abnormalities and esophageal abnormalities were identified. Using medical record information and client interviews, the relationship between these comorbidities and postoperative survival (primary outcome measure) and postoperative complications (secondary outcome measure) was identified. RESULTS: Dogs that had surgical correction of ILP had a 2.6-fold reduction in the hazard of death throughout the study period (HR = 2.6; 95% CI: 1.34-4.84, P = .006). Owner assessed patient quality of life (10-point scale) increased by an average of 4.1 ± 1.4 units immediately postoperatively, and 4.9 ± 0.9 units until death or followup compared with preoperative values. Thirty-five of 72 dogs available for followup had evidence of diffuse neurologic comorbidities. Overall complication rate for dogs with neurologic comorbidities was 74%, compared with 32% for dogs without neurologic comorbidities. Presence of any neurologic comorbidity was associated with a significantly greater odds of any complication (OR = 4.04; 95% CI: 1.25-13.90, P = .019) as well as recurring complications (OR = 8.00; 95% CI: 1.49-54.38; P = .015). CONCLUSION: Surgical correction of ILP was positively associated with survival, and dogs with neurologic comorbidities were at greater risk for developing postoperative complications.

Bone marrow transcriptome and epigenome profiles of equine common variable immunodeficiency patients unveil block of B lymphocyte differentiation.

Common variable immunodeficiency (CVID) is a late-onset humoral deficiency characterized by B lymphocyte dysfunction or loss, decreased immunoglobulin production, and recurrent bacterial infections. CVID is the most frequent human primary immunodeficiency but still presents challenges in the understanding of its etiology and treatment. CVID in equine patients manifests with a natural impairment of B lymphocyte differentiation, and is a unique model to identify genetic and epigenetic mechanisms of disease. Bone marrow transcriptome analyses revealed decreased expression of genes indicative of the pro-B cell differentiation stage, importantly PAX5 (p≤0.023). We hypothesized that aberrant epigenetic regulation caused PAX5 gene silencing, resulting in the late-onset and non-familial manifestation of CVID. A significant increase in PAX5 enhancer region methylation was identified in equine CVID patients by genome-wide reduced-representation bisulfite sequencing and bisulfite PCR sequencing (p=0.000). Thus, we demonstrate that integrating transcriptomics and epigenetics in CVID enlightens potential mechanisms of dysfunctional B lymphopoiesis or function.

Membrane perturbing actions of HIV type 1 glycoprotein 41 domains are inhibited by helical C-peptides.

To study the membrane actions of various domains of HIV-1 glycoprotein 41,000 (gp41), synthetic peptides were prepared corresponding to the N-terminal fusion region (FP; gp41 residues 519-541), the nearby N-leucine zipper domain (N-peptides; DP-107; gp41 residues 560-597), the C-leucine zipper domain (C-peptides; DP-178; gp41 residues 645-680), and the viral envelope adjacent domain that partially overlaps DP-178 (Pre-TM; gp41 residues 671-690). With erythrocytes, FP, DP-107, and Pre-TM induced hemolysis and cell aggregation; the order for hemolytic activity was Pre-TM > FP > DP-107, but each was equally effective in aggregating cells at the highest peptide concentrations tested. DP-178 produced neither hemolysis nor aggregation, but efficiently reduced FP-, DP-107-, and Pre-TM-induced membrane actions. Fourier transform infrared spectroscopy indicated that the membrane perturbations of Pre-TM, as well as the ability of DP-178 to block membrane activities of other gp41 domains, are dependent on Pre-TM and DP-178 each maintaining helical conformations and tryptophans at residues 673, 677, and 679. These results suggest that the corresponding N-terminal fusion, N-leucine zipper, and viral membrane-adjacent regions of HIV-1 gp41 may similarly promote key membrane perturbations underlying the merging of the viral envelope with the cell surface. Further, the antiviral mechanism of exogenous DP-178 (clinically approved enfuvirtide) may be partially explained by its coordinate inhibition of the fusogenic actions of the FP, DP-107, and Pre-TM regions of gp41.

To what extent have high schools in California been able to implement state-mandated nutrition standards?

PURPOSE: To determine extent and factors associated with implementation of California's school nutrition standards 1 year after standards became active. METHODS: Information on competitive foods and beverages available in schools was collected from a representative sample of 56 public high schools in California. Adherence to nutrition standards was calculated for each item and summarized for each school by venue. The association between schools' sociodemographic characteristics and adherence to standards was determined by multivariate analysis. RESULTS: The majority of schools were adhering to the required beverage standards. None of the schools selling competitive foods were 100% adherent to the food standards. Adherence to both standards tended to be highest in food service venues. In univariate analyses, percent nonwhite enrollment, population density, percent free/reduced-price (FRP) meal eligibility, and school size were significantly correlated with the beverage adherence rate. Percent nonwhite enrollment and population density remained significant in the multivariate regression model. Percent nonwhite enrollment and percent FRP meal eligibility were significantly correlated with the food adherence rate in univariate analysis, but neither remained significant in the multiple regression model. CONCLUSIONS: California high schools are making progress toward implementation of the state nutrition standards. Beverage standards appear easier to achieve than nutrient-based food standards. Additional support is needed to provide schools with resources to implement and monitor these policies. Simpler standards and/or a reduction in the foods and beverages sold could better enable schools to achieve and monitor adherence.