Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs.

In the past two decades, average litter size (ALS) in Entlebucher Mountain dogs decreased by approximately 0.8 puppies. We conducted a GWAS for ALS using the single-step methodology to take advantage of 1632 pedigree records, 892 phenotypes and 372 genotypes (173 662 markers) for which only 12% of the dogs had both phenotypes and genotypes available. Our analysis revealed associations towards the growth differentiation factor 9 gene (GDF9), which is known to regulate oocyte maturation. The trait heritability was estimated at 43.1%, from which approximately 15% was accountable by the GDF9 locus alone. Therefore, markers flanking GDF9 explained approximately 6.5% of the variance in ALS. Analysis of WGSs revealed two missense substitutions in GDF9, one of which (g.11:21147009G>A) affected a highly conserved nucleotide in vertebrates. The derived allele A was validated in 111 dogs and shown to be associated with decreased ALS (-0.75 ± 0.22 puppies per litter). The variant was further predicted to cause a proline to serine substitution. The affected residue was immediately followed by a six-residue deletion that is fixed in the canine species but absent in non-canids. We further confirmed that the deletion is prevalent in the Canidae family by sequencing three species of wild canids. Since canids uniquely ovulate oocytes at the prophase stage of the first meiotic division, requiring maturation in the oviduct, we conjecture that the amino acid substitution and the six-residue deletion of GDF9 may serve as a model for insights into the dynamics of oocyte maturation in canids.

Moreau Strain Bacillus Calmette-Guérin Low Versus Standard Dose in the Treatment of High-Grade T1 Bladder Cancer: A Retrospective Observational Cohort Study.

PURPOSE: To evaluate recurrence, progression, and cancer-specific mortality of high-grade T1 non-muscle-invasive bladder cancer by assessing receipt of a low dose of the underexplored bacillus Calmette-Guérin (BCG) Moreau strain in a retrospective observational cohort study. PATIENTS AND METHODS: From January 2006 to December 2015, a total of 219 consecutive patients with high-grade T1 non-muscle-invasive bladder cancer received half-dose (40 mg; n = 109) or standard-dose (80 mg; n = 110) BCG Moreau strain after transurethral resection of the bladder. BCG therapy was initiated 2 or 3 weeks after transurethral resection of the bladder using the following protocol: 6 weekly doses, 12 monthly, 4 once every 3 months, and 2 once every 6 months, with a total of 24 doses. RESULTS: Comparing the half-dose and standard-dose treatment groups, in a median follow-up of 74.6 months, recurrence (n = 51, 46.8% vs. n = 60, 54.5%, P = .28), progression (n = 18, 16.5% vs. n = 16, 14.5%, P = .69), and disease-specific mortality (n = 9, 8.3% vs. n = 5, 4.5%, P = .26) were not significantly different on Kaplan-Meier curves and log-rank test, respectively. Charlson comorbidity index was an independent predictor of death from disease (hazard ratio = 1.341; 95% confidence interval, 1.033-1.740; P = .0274); no predictor of recurrence or progression was identified. Treatment intolerance occurred in 1 (0.9%) versus 6 (5.4%) patients (P = .12), respectively. No hospital admission or systemic BCG toxicity was reported. CONCLUSION: To our knowledge, this is the largest low-dose Moreau BCG strain study in high-grade T1 scenario. A half dose of BCG Moreau strain might be safe and effective in terms of tumor control, progression, or cancer-specific mortality with a low complication rate, which is central to the worldwide scenario of BCG shortage, and can help regulatory agencies approve efficient daughter BCG strains.

Effects of ß-Glucans Ingestion on Alveolar Bone Loss, Intestinal Morphology, Systemic Inflammatory Profile, and Pancreatic ß-Cell Function in Rats with Periodontitis and Diabetes.

This study aimed to evaluate the effects of ß-glucan ingestion (Saccharomyces cerevisiae) on the plasmatic levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), alveolar bone loss, and pancreatic ß-cell function (HOMA-BF) in diabetic rats with periodontal disease (PD). Besides, intestinal morphology was determined by the villus/crypt ratio. A total of 48 Wistar rats weighing 203 ± 18 g were used. Diabetes was induced by the intraperitoneal injection of streptozotocin (80 mg/kg) and periodontal inflammation, by ligature. The design was completely randomized in a factorial scheme 2 × 2 × 2 (diabetic or not, with or without periodontitis, and ingesting ß-glucan or not). The animals received ß-glucan by gavage for 28 days. Alveolar bone loss was determined by scanning electron microscopy (distance between the cementoenamel junction and alveolar bone crest) and histometric analysis (bone area between tooth roots). ß-glucan reduced plasmatic levels of TNF-α in diabetic animals with PD and of IL-10 in animals with PD (p < 0.05). ß-glucan reduced bone loss in animals with PD (p < 0.05). In diabetic animals, ß-glucan improved ß-cell function (p < 0.05). Diabetic animals had a higher villus/crypt ratio (p < 0.05). In conclusion, ß-glucan ingestion reduced the systemic inflammatory profile, prevented alveolar bone loss, and improved ß-cell function in diabetic animals with PD.