Effects of end-stage osteoarthritis on markers of skeletal muscle Long INterspersed Element-1 activity

Objective: Long INterspersed Element-1 (L1) is an autonomous transposable element in the genome. L1 transcripts that are not reverse transcribed back into the genome can accumulate in the cytoplasm and activate an inflammatory response via the cyclic GMP-AMP (cGAS)-STING pathway. We examined skeletal muscle L1 markers as well as STING protein levels in 10 older individuals (63 ± 11 y, BMI= 30.2 ± 6.8 kg/m2) with end-stage osteoarthritis (OA) undergoing total hip (THA, n= 4) or knee (TKA, n= 6) arthroplasty versus 10 young, healthy comparators (Y, 22 ± 2 y, BMI= 23.2 ± 2.5 kg/m2). For OA, muscle was collected from surgical (SX) and contralateral (CTL) sides whereas single vastus lateralis samples were collected from Y. Results: L1 mRNA was higher in CTL and SX compared to Y (p \u3c 0.001 and p= 0.001, respectively). Protein expression was higher in SX versus Y for ORF1p (p= 0.002) and STING (p= 0.022). While these data are preliminary due to limited n-sizes and the lack of a BMI-matched younger control group, higher L1 mRNA expression, ORF1p and STING protein are evident in older versus younger adults. More research is needed to determine whether cGAS-STING signaling contributes to heightened muscle inflammation during aging and/or OA

Impact of Protein and Carbohydrate Supplementation on Musculoskeletal Injuries in Army Initial Entry Training Soldiers

This project investigated whey protein and/or carbohydrate supplementation effects on musculoskeletal injury (MSI) outcomes. Four groups of Initial Entry Training soldiers consumed either: (1) one protein (38.6 g, 293 kcal); (2) one carbohydrate (63.4 g, 291 kcal); (3) two protein (77.2 g, 586 kcal); or (4) two carbohydrate servings/day (126.8 g, 582 kcal) after physical training and before bed, or before bed only. Odds Ratio, Chi-square and Wilcoxon ranked-sum test compared supplementation/no supplementation, number of servings, and protein/carbohydrate for MSI and limited/missed duty rates and limited/missed training days. Non-matched pairs group averages were compared to 2015/2016 historical data. Non-supplemented soldiers were approximately 5× more likely to sustain a MSI (χ2 = 58.48, p < 0.001) and 4× more likely to miss training (χ2 = 9.73, p = 0.003) compared to two servings. Non-supplemented soldiers missed five additional training days compared to two servings (W = 6059.5, p = 0.02). Soldiers consuming one serving were approximately 3× more likely to sustain a MSI than two servings (χ2 = 9.55, p = 0.002). There was no difference in limited/missed duty rates or limited/missed training days between consuming one or two servings. There was no difference between consuming one serving versus no supplementation or protein versus carbohydrate supplementation for any outcome variable. Soldiers consuming 2 servings/day of protein or carbohydrate had lower MSI rates, limited/missed duty rates, and limited/ missed training days compared to non-supplemented soldiers

Markers of Bone Health and Impact of Whey Protein Supplementation in Army Initial Entry Training Soldiers: A Double-Blind Placebo-Controlled Study

Training civilians to be soldiers is a challenging task often resulting in musculoskeletal injuries, especially bone stress injuries. This study evaluated bone health biomarkers (P1NP/CTX) and whey protein or carbohydrate supplementations before and after Army initial entry training (IET). Ninety male IET soldiers participated in this placebo-controlled, double-blind study assessing carbohydrate and whey protein supplementations. Age and fat mass predicted bone formation when controlling for ethnicity, explaining 44% (p < 0.01) of bone formation variations. Age was the only significant predictor of bone resorption (p = 0.02) when controlling for run, fat, and ethnicity, and these factors together explained 32% of the variance in bone resorption during week one (p < 0.01). Vitamin D increased across training (p < 0.01). There was no group by time interaction for supplementation and bone formation (p = 0.75), resorption (p = 0.73), Vitamin D (p = 0.36), or calcium (p = 0.64), indicating no influence of a supplementation on bone biomarkers across training. Age, fitness, fat mass, and ethnicity were important predictors of bone metabolism. The bone resorption/formation ratio suggests IET soldiers are at risk of stress injuries. Male IET soldiers are mildly to moderately deficient in vitamin D and slightly deficient in calcium throughout training. Whey protein or carbohydrate supplementations did not affect the markers of bone metabolism

Effect of Whey Protein Supplementation on Physical Performance and Body Composition in Army Initial Entry Training Soldiers

We investigated the effects of whey protein (WP) supplementation on body composition and physical performance in soldiers participating in Army Initial Entry Training (IET). Sixty-nine, male United States Army soldiers volunteered for supplementation with either twice daily whey protein (WP, 77 g/day protein, ~580 kcal/day; n = 34, age = 19 ± 1 year, height = 173 ± 6 cm, weight = 73.4 ± 12.7 kg) or energy-matched carbohydrate (CHO) drinks (CHO, 127 g/day carbohydrate, ~580 kcal/day; n = 35, age = 19 ± 1 year, height = 173 ± 5 cm, weight = 72.3 ± 10.9 kg) for eight weeks during IET. Physical performance was evaluated using the Army Physical Fitness Test during weeks two and eight. Body composition was assessed using 7-site skinfold assessment during weeks one and nine. Post-testing push-up performance averaged 7 repetitions higher in the WP compared to the CHO group (F = 10.1, p < 0.001) when controlling for baseline. There was a significant decrease in fat mass at post-training (F = 4.63, p = 0.04), but no significant change in run performance (F = 3.50, p = 0.065) or fat-free mass (F = 0.70, p = 0.41). Effect sizes for fat-free mass gains were large for both the WP (Cohen’s d = 0.44) and CHO (Cohen’s d = 0.42) groups. WP had a large effect on fat mass (FM) loss (Cohen’s d = −0.67), while CHO had a medium effect (Cohen’s d = −0.40). Twice daily supplementation with WP improved push-up performance and potentiated reductions in fat mass during IET training in comparison to CHO supplementation

Tuberculosis Contacts but Not Patients Have Higher Gamma Interferon Responses to ESAT-6 than Do Community Controls in The Gambia

The Mycobacterium tuberculosis antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-γ) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-γ assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further

ICOS promotes IL-17 synthesis in colonic intraepithelial lymphocytes in IL-10−/− mice

In the absence of IL-10, colonic inflammation ensues, which is characterized by high levels of IL-17. Here, we demonstrate a direct correlation between ICOS expression and IL-17 production in cIELs. IL-10−/− mice had increased numbers of cIELs and greater colon weight. Although the CD69 early activation antigen was expressed on cIELs from normal and IL-10−/− mice, ICOS was expressed only on cIELs from IL-10−/− mice. IL-17-producing cells in IL-10−/− mice consisted of CD4+ and CD8+ cIELs; however, CD4+ cells were the predominant IL-17-producing cell population. Culture of cIELs from IL-10−/− mice with IL-23 resulted in an increase in ICOS and IL-17 expression, whereas IL-10 suppressed expression of ICOS and IL-17. This occurred in primary cultures and recall stimulation experiments. The ICOS ligand B7RP-1 was up-regulated on colonic epithelial cells and on a population of large granular leukocytes during inflammation. Culture of cIELs with B7RP-1+ DCs enhanced IL-17A production from normal cIELs but failed to do so using cIELs from ICOS−/− mice. In vivo treatment of IL-10−/− mice with antibody to ICOS resulted in a significant reduction in colonic pathology. These findings implicate ICOS as an activational signal of Th17 cells during chronic intestinal inflammation, and they suggest that under some conditions, control of ICOS expression may help to suppress chronic intestinal inflammation