Development of septic polysynovitis and uveitis in foals experimentally infected with \u3ci\u3eRhodococcus equi\u3c/i\u3e

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent R. equi using inocula of 1×108 CFU (high inoculum; n = 16) or 1×107 CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. R. equi was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Peer reviewe

Development of septic polysynovitis and uveitis in foals experimentally infected with \u3ci\u3eRhodococcus equi\u3c/i\u3e

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent R. equi using inocula of 1×108 CFU (high inoculum; n = 16) or 1×107 CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. R. equi was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease

Synovitis with hyperplasia of synoviocytes, suppurative inflammation, and fibrinocellular joint exudate including macrophage (arrow) containing multiple intracytoplasmic, 2 x 3 μm coccobacilli in a foal that developed polysynovitis after intratracheal infection with virulent <i>R</i>. <i>equi</i>.

<p>Hematoxylin and eosin, bar = 10 μm.</p

Mean (±SD) rectal temperature of foals experimentally infected with virulent <i>R</i>. <i>equi</i>.

<p>Foals were infected with a high inoculum (1 × 10⁸ CFU; n = 16) or a low inoculum (1 × 10⁷ CFU; n = 12). *Indicates a significantly higher rectal temperature relative to day 0 and relative to the temperature of foals infected with the low inoculum.</p

Comparison of mean (± SD) total protein concentration in aqueous humor and synovial fluid between inocula (high vs low) and presence or absence of clinically detectable polysynovitis or uveitis in 28 foals experimentally infected with <i>R</i>. <i>equi</i>.

<p>Comparison of mean (± SD) total protein concentration in aqueous humor and synovial fluid between inocula (high vs low) and presence or absence of clinically detectable polysynovitis or uveitis in 28 foals experimentally infected with <i>R</i>. <i>equi</i>.</p

Kaplan-Meier curve of the cumulative probability of developing polysynovitis in foals infected intratracheally with a high inoculum (1 × 10⁸ CFU; n = 16) or a low inoculum (1 × 10⁷ CFU; n = 12) of virulent <i>R</i>. <i>equi</i>.

<p>Kaplan-Meier curve of the cumulative probability of developing polysynovitis in foals infected intratracheally with a high inoculum (1 × 10⁸ CFU; n = 16) or a low inoculum (1 × 10⁷ CFU; n = 12) of virulent <i>R</i>. <i>equi</i>.</p

Development of septic polysynovitis and uveitis in foals experimentally infected with <i>Rhodococcus equi</i>

<div><p><i>Rhodococcus equi</i> is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with <i>R</i>. <i>equi</i> and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with <i>R</i>. <i>equi</i> and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent <i>R</i>. <i>equi</i> using inocula of 1×10⁸ CFU (high inoculum; n = 16) or 1×10⁷ CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. <i>R</i>. <i>equi</i> was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease.</p></div