Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis.

OBJECTIVE: Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte-driven inflammation through a transforming growth factor ß1-dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. METHODS: Collagen-induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss-of-function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C-reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. RESULTS: Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin-6 in the blood. Similarly, rs12212067 (a single-nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. CONCLUSION: Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage.

Effects of forage species and poultry litter application timing on forage preference by horses.

Bermudagrass ( L.) is a familiar forage in the equine industry and teff () is gaining popularity as well. However, it is unclear if the application of poultry litter as a fertilizer affects palatability of these forages in horses. Therefore, the objective of this study was to determine if forage species and timing of litter application as a fertilizer has an effect on preference by horses. Hay treatments were arranged in a 2 × 3 factorial treatment arrangement consisting of teff and bermudagrass harvested after no poultry litter application (NL), poultry litter applied to stubble immediately after removal of the previous cutting (L0), or poultry litter applied 14 d after the previous cutting (L14). Mature, stock-type geldings ( = 5; 480 ± 52.9 kg) were used in this study arranged as a balanced incomplete block design. Horses were offered different combinations of 4 of the 6 total forages daily for 3 d in each of 3 evaluation periods that immediately followed a 10-d adaptation period. Each forage was offered at half of the total daily DMI as measured during the last 5 d of the 10-d adaptation period to encourage selection among the 4 forages. Each hay offered was randomly allocated to a corner and suspended in hay nets over muck buckets in the corners of each stall. Horses were individually housed in 3.6- by 3.6-m indoor stalls with sand bedding and access to 3.6- by 7.6-m outdoor runs. Along with hay, horses were offered oats twice daily at 0.125% of BW at each feeding. Dry matter intake was greater ( < 0.01) for bermudagrass than for teff and for NL and L0 treatments compared with L14 treatments. Horses spent more ( < 0.01) time consuming bermudagrass compared with teff. However, there were no differences ( ≥ 0.25) in time spent consuming hay across litter treatments. Therefore, horses may prefer bermudagrass to teff and later application of poultry litter may affect voluntary intake by horses. However, all forages were mature, which may have impacted total intake and preference.

Digestibility, apparent mineral absorption, and voluntary intake by horses fed alfalfa, tall fescue, and caucasian bluestem.

Alfalfa (Medicago sativa L.), low-endophyte (< 5%) tall fescue (Festuca arundinacea Schreb.), and caucasian bluestem (Bothriochloa caucasica [Trin.] C.E. Hubbard) were fed as chopped hay to six Arabian geldings (BW 441 kg; SE 2) in intake and digestibility experiments to determine nutritional value for horses at maintenance. Each experimental design was a replicated Latin square. Alfalfa was higher in DM and CP digestibility, IVDMD, apparent absorption of Ca, K, and S, and voluntary intake than the grasses (P < .05). Caucasian bluestem was higher in Zn but was lower in CP, TNC, Mg, P, K, S, and Cu concentrations than tall fescue. Crude protein digestibility and apparent absorption of Mg, K, and S were higher (P < .05) for tall fescue than for caucasian bluestem. Geldings fed alfalfa for ad libitum intake had higher serum concentrations of vitamin A, blood urea nitrogen, P, S, and Cu than geldings fed grass hays. Serum Zn was higher (P < .05), whole blood Se tended to be higher (P < .06), and BUN was lower (P < .05) in geldings fed caucasian bluestem than in those fed tall fescue. All forages met requirements for CP, Ca, Mg, K, and Fe when fed for ad libitum intake but were deficient in Cu for horses at maintenance. Caucasian bluestem was borderline in CP and was deficient in P but was the only forage that met the Zn requirement for the horses. Based on these results, caucasian bluestem could be a useful hay for horses but may require supplementation of CP and P.