Interleukin-6 ablation does not alter morphofunctional heart characteristics but modulates physiological and inflammatory markers after strenuous exercise.

Interleukin-6 (IL-6) is associated with pathological cardiac hypertrophy and can be dramatically increased in serum after an acute strenuous exercise session. However, IL-6 is also associated with the increased production and release of anti-inflammatory cytokines and the inhibition of tumor necrosis factor-alpha (TNF-α) after chronic moderate exercise. To elucidate the relevance of IL-6 in inflammatory and hypertrophic signaling in the heart in response to an acute strenuous exercise session, we combined transcriptome analysis using the BXD mice database and exercised IL-6 knockout mice (IL-6KO). Bioinformatic analysis demonstrated that low or high-levels of Il6 mRNA in the heart did not change the inflammation- and hypertrophy-related genes in BXD mice strains. On the other hand, bioinformatic analysis revealed a strong positive correlation between Il6 gene expression in skeletal muscle with inflammation-related genes in cardiac tissue in several BXD mouse strains, suggesting that skeletal muscle-derived IL-6 could alter the heart's intracellular signals, particularly the inflammatory signaling. As expected, an acute strenuous exercise session increased IL-6 levels in wild-type, but not in IL-6KO mice. Despite not showing morphofunctional differences in the heart at rest, the IL-6KO group presented a reduction in physical performance and attenuated IL-6, TNF-α, and IL-1beta kinetics in serum, as well as lower p38MAPK phosphorylation, Ampkalpha expression, and higher Acta1 and Tnf gene expressions in the left ventricle in the basal condition. In response to strenuous exercise, IL-6 ablation was linked to a reduction in the pro-inflammatory response and higher activation of classical physiological cardiac hypertrophy proteins.

Protein blend and casein supplementations before inactive phase similarly activate mechanistic target of rapamycin signaling in rat skeletal muscle.

During overnight sleep, the longest postabsorptive and inactive phase of the day causes protein catabolism and loss. However, the daytime ingestion of dairy proteins has been shown to stimulate muscle protein synthesis and growth. This study compared the effects of pre-sleep supplementation of a protein blend (PB) composed of micellar casein (MCa) and whey protein (1:1) versus isolate MCa on the plasma levels of branched-chain amino acids (BCAAs) and the activation of the mechanistic target of rapamycin (mTOR) signaling, a critical intracellular pathway involved in the regulation of muscle protein synthesis. After 10 h of fasting during the active phase, rats were fed with a single dose of PB or MCa (5.6 g protein/kg of body mass) by gavage, and samples of blood and gastrocnemius muscle were collected at 30, 90, and 450 min. PB and MCa supplementations induced an increase (~3-fold, P < 0.001) of plasma BCAAs at 30 and 90 min. Most importantly, the stimulatory phosphorylation levels of mTOR and its downstream target p70 ribosomal protein S6 kinase (p70S6K) were similarly higher (~2.5-fold, P < 0.001) 30 and 90 min after MCa and PB. Plasma levels of leucine, isoleucine, valine, and overall BCAAs were correlated with the activation of mTOR (P < 0.001) and p70S6K (P < 0.001). MCa and PB supplementations before the inactive phase of rats resulted in an anabolic milieu in the skeletal muscle by inducing a transient increase in plasma BCAAs and a similar activation of the mTOR/p70S6K axis.

Development and Implementation of a Clinical Pathway to Reduce Inappropriate Admissions Among Patients with Community-Acquired Pneumonia in a Private Health System in Brazil: An Observational Cohort Study and a Promising Tool for Efficiency Improvement.

PURPOSE: Patients with community-acquired pneumonia (CAP) at low risk of death by CURB-65 scoring system are usually unnecessarily treated as inpatients generating additional economic and clinical burden. We aimed to implement an evidence-based clinical pathway to reduce hospital admissions of low-risk CAP and investigate factors related to mortality and readmissions within 30 days. PATIENTS AND METHODS: From November 2015 to August 2017, a clinical pathway was implemented at 20 hospitals. We included patients aged >18 years, with a diagnosis of CAP by the attendant physician. The main outcome was the monthly proportion of low-risk CURB-65 admission after the implementation of the clinical pathway. Logistic regression models were performed to assess variables associated with mortality and readmission in the admitted population within 30 days. RESULTS: We included 10,909 participants with suspected CAP. The proportion of low-risk CAP admitted decreased from 22.1% to 12.8% in the period. Among participants with low risk, there has been no perceptible increase in deaths (0.80%) or readmissions (6.92%). Regression analysis identified that CURB-65 variables, presence of pleural effusion (OR= 1.74; 95%CI=1.08-2.8; p=0.02) and leucopenia (OR= 2.47; 95%CI=1.11-5.48; p=0.02) were independently associated with 30-day mortality, whereas a prolonged hospital stay (OR= 2.09; 95%CI=1.14-3.83; p=0.01) was associated with 30-day readmission in the low-risk population. CONCLUSION: The implementations of a clinical pathway diminished the proportion of low-risk CAP admissions with no apparent increase in clinical outcomes within 30 days. Nonetheless, additional factors influence the clinical decision about the site of care management in low-risk CAP.

Positive effects of total recovery period on anti- and pro-inflammatory cytokines are not linked to performance re-establishment in overtrained mice.

The association between excessive training sessions (i.e., overtraining/OT) and periods of inadequate recovery is linked to the nonfunctional overreaching (NFOR) state, which is defined as an unexplained decrement or stagnation of performance. The cytokine hypothesis of OT considers that pro-inflammatory cytokines are responsible by the NFOR state-induced performance decrement. Investigations using rodent models of OT verified increased levels of pro-inflammatory cytokines in hypothalamus, liver, serum and skeletal muscle samples. Recently, our research group observed that a 2-week total recovery period was not able to re-establish the NFOR state-induced performance decrement. As the responses of anti- and pro-inflammatory cytokines were not measured, we aimed to investigate the effects of 2-week total recovery period on the protein contents of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in serum and skeletal muscle samples of overtrained mice. Also, a bioinformatics analysis was performed to investigate the correlations of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in skeletal muscle with locomotor activity. In summary, the 2-week total recovery period upregulated the anti-inflammatory cytokines and normalized the pro-inflammatory cytokines without a concomitant re-establishment of performance.

Central venous saturation: a prognostic tool in cardiac surgery patients.

BACKGROUND: Central venous oxygen saturation (ScvO(2)) is a valuable prognostic marker in sepsis. However, its value in cardiac surgery has not been assessed yet. This study aimed at evaluating ScvO(2) as a tool for predicting short-term organ dysfunction (OD) after cardiac surgery. METHODS: A prospective cohort including cardiac surgery patients submitted to a goal-oriented therapy to maintain ScvO(2) above 70% was studied. Postoperative blood samples collected at 30 minutes (T1), 6 hours (T2), and 24 hours (T3) for ScvO(2) measurement were selected to further analysis. Two groups were formed according to the absence (G0) or presence (G1) of OD defined as a Sequential Organ Failure Assessment (SOFA) score >or=5 on the third postoperative day. A logistic regression analysis was performed to identify the variables independently associated with OD on the third postoperative day. RESULTS: From the 246 patients included, 54 (22%) developed OD and were defined as G1. The mortality rates in G0 and G1 were 1.6% and 31.5%, respectively (P < .001). In the comparative analysis between G0 and G1, the ScvO(2) values were remarkably lower in G1 at T1 (66.2 +/- 9.2 vs 62.3 +/- 11.6; P = .009), T2 (69.6 +/- 5.9 vs 63.5 +/- 9.4; P