Stimulated Muscle Contractions Regulate Membrane-Bound and Soluble TLR4 to Prevent LPS-Induced Signaling and Myotube Atrophy in Skeletal Muscle Cells

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) contributes to chronic inflammation and causes upregulation of muscle atrophy signaling pathways. Exercise can suppress LPS/TLR4 axis activation by reducing the expression of TLR4 on immune cells. It is unknown how this regulation occurs, and it is not clear how exercise affects TLR4 on skeletal muscle. PURPOSE: To uncover the nature and mechanisms by which exercise affects TLR4 expression and intracellular signaling using cell culture models and human experiments. METHODS: C2C12 myotubes were subjected to electrical pulse stimulation (EPS) with and without subsequent treatment with 500 ng/mL lipopolysaccharide (LPS) along with corresponding control conditions. To investigate the effect of muscle contraction on the regulation of TLR4 in-vivo, we analyzed PBMC and serum samples from eight recreationally active men that completed 60-minutes of cycling at a moderate intensity (65% of VO2max). RESULTS: In-vitro, LPS decreased membrane-bound TLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, stimulated muscle contractions decreased membrane-bound TLR4, increased soluble TLR4 (sTLR4), and prevented LPS-induced signaling and myotube atrophy. In human participants, a single bout of moderate-intensity exercise decreased membrane-bound TLR4 on PBMCs and increased serum-borne sTLR4. CONCLUSION: These experiments support exercise may exert a novel anti-catabolic/ anti-inflammatory effect by increasing sTLR4 and decreasing TLR4 expressed on the muscle membrane. These results could help improve interventions for conditions associated with TLR4-mediated inflammation and muscle atrophy, such as diabetes, sarcopenia, and cancer cachexia

Comparison of Supine and Vertical Bioimpedance Measurements in Young Adults

Topics in Exercise Science and Kinesiology Volume 3: Issue 1, Article 11, 2022. Bioelectrical impedance analysis (BIA) methods estimate health parameters such as phase angle (PhA) and body fat percentage (%BF) from various positional and electrode configurations. PhA and %BF are known biological markers of cellular and physical health, respectively, and can be used to predict various health-related conditions and therefore require accurate assessment. The purpose of this study was to evaluate the effect of body position during BIA by investigating the difference and agreement between PhA and %BF using RJL (supine) and InBody (vertical) analyzers. Thirty-eight young adults (23.4±4.1 yrs.) volunteered and underwent body composition assessments by both analyzers. Difference and agreement in assessments of PhA and %BF between analyzers were assessed using paired samples t-tests and Lin’s concordance correlation coefficient (rc), respectively. RJL’s PhA (7.15±0.84°) exceeded InBody’s (6.11±0.74°), p\u3c0.001, and had poor agreement (rc =0.47). RJL’s %BF (23.0±6.8%) was similar to InBody’s (23.1±7.4%), p=0.813, and had substantial agreement (rc =0.95). Both analyzers estimated %BF similarly and may be interchangeable for this purpose, thus demonstrating no effect of body position on the estimation of %BF with these BIA devices. An individual\u27s PhA may be underestimated if measured in the vertical position and compared to supine reference values. Current reference values for PhA are based on measurements in the supine position, so until vertical reference values of PhA are available, caution is urged when interpreting PhA from vertical BIA assessments

More flexible brain activation underlies cognitive reserve in older adults

Abstract The goal of this study was to identify the brain mechanisms underlying cognitive reserve using a parametric n-back working memory (WM) task in a sample of healthy older adults. We first identified the WM-related activations associated with years of education and then tested whether these activations mitigated the detrimental impact of age on cognition. Thirty-nine older adults received a magnetic resonance imaging examination while completing an n-back task with different levels of WM load (0-, 1- vs. 2-back). Results show that more education is associated with lower activation of the left medial superior frontal gyrus (BA8) in the 1-back condition and a greater activation of the right caudate nucleus in the 2-back condition. The caudate and frontal activations are task-positive and task-negative regions, respectively. Moderation analyses indicate that the effect of age on performance is less detrimental in participants with higher caudate activation in the 2-back condition. Overall, these results suggest that cognitive reserve is explained by a superior ability to flexibly engage greater or novel activation as cognitive demand increases

The Effect of Quercetin on Bone Turnover Markers, Inflammatory Markers, and Bone Mineral Density in Postmenopausal Women: A Double-Blind Placebo-Controlled Investigation

Maintaining optimal bone health prevents major bone disorders (e.g., osteoporosis) and prolongs longevity. Quercetin is a plant-based flavonoid that is suggested to have anti-inflammatory effects and may improve bone health. PURPOSE: To investigate the effects of quercetin supplementation over 90-days on prominent bone turnover markers (BTMs), inflammatory markers, bone mineral density (BMD), body composition, and physical functioning in postmenopausal women. METHODS: Thirty-three healthy, nonosteoporotic, postmenopausal women (59.2±7.0 years) participated in a double-blind, placebo-controlled investigation. Participants were randomized into one of two supplement groups: 1) 500 mg of quercetin (QUE) once daily or 2) 500 mg of methylcellulose (placebo; PLB) once daily. Pre- and post-testing visits included assessments of BTMs (i.e., osteocalcin [OC], procollagen type-I N-terminal propeptide [PINP], and type-I collagen cross-linked C-terminal telopeptide [CTX]), inflammatory markers (i.e., interleukin [IL]-6, tumor necrosis factor-alpha [TNF-a], and C-reactive protein [CRP]), BMD measurements, body composition measurements (i.e., body fat percentage), and physical function. RESULTS: The QUE group increased OC (p=0.016; d=0.89), PINP (p=0.030; d=0.64), and CTX (p=0.023; d=0.91) levels and decreased IL-6 (p=0.045; d=0.73) and TNF-a (p=0.021; d=0.90) levels compared to PLB. CRP (p=0.448; d=0.34), BMD, body composition, and physical function remained unchanged. CONCLUSION: The results indicate that QUE may maintain optimal bone health by mediating bone formation and decreasing pro-inflammatory cytokines

New Multisite Bioelectrical Impedance Device Compared to Hydrostatic Weighing and Skinfold Body Fat Methods

International Journal of Exercise Science 13(4): 1718-1728, 2020. The purpose of this study was to compare the Skulpt Chisel™ to seven-site skinfold (SKF) and hydrostatic weighing (HW) body fat percentage (%BF) estimates. Twenty-six participants (aged 24 ± 4 years; BMI 23.1 ± 3.5 kg∙m-2) were assessed. Significant differences in %BF estimates were found for all methodological pairings; p \u3c 0.05. The SKF method underestimated %BF compared to HW (-2.52 ± 3.42 %BF). The Skulpt Chisel™ overestimated %BF compared to both HW (3.38 ± 6.10 %BF) and SKF (5.90 ± 5.26 %BF). Limits of agreement comparing HW to Skulpt Chisel™ indicated a difference between 95% confidence interval bounds (Upper bound: 5.84 %BF, Lower bound 0.92 %BF) and for HW to SKF (Upper bound: -1.14 %BF, Lower bound: -3.91 %BF). Regression analysis showed no significant bias for any methodological pairing; (p \u3e 0.05). In conclusion, the Skulpt Chisel™ method should be used with caution when evaluating %BF of adults with similar demographics reported in this study

Where are commodity crops certified, and what does it mean for conservation and poverty alleviation?

Voluntary sustainability standards have expanded dramatically over the last decade. In the agricultural sector, such standards aim to ensure environmentally and socially sustainable production of a variety of commodity crops. However, little is known about where agricultural certification operates and whether certified lands are best located for conserving the world's most important biodiversity and benefiting the most vulnerable producers. To examine these questions we developed the first global map of commodity crop certification, synthesizing data from over one million farms to reveal the distribution of certification in unprecedented detail. It highlights both geographical clusters of certification as well as spatial bias in the location of certification with respect to environmental, livelihood and physical variables. Excluding organic certification, for which spatial data were not available, most certification of commodity crops is in tropical regions. Certification appears to be concentrated in areas important for biodiversity conservation, but not in those areas most in need of poverty alleviation, although there were exceptions to each of these patterns. We argue that the impact of sustainability standards could be increased by identifying places where it would be most beneficial to strengthen, consolidate, and expand certification. To achieve this, standards organizations will need to undertake more rigorous collection of spatial data, and more detailed analysis of their existing reach and impacts, with attention to potential trade-offs between different objectives. Efforts to promote spatial prioritization will require new partnerships to align specific conservation aims with the interests and capabilities of farmers

Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia

The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages

Hemodynamic-GUIDEd management of Heart Failure (GUIDE-HF)

In that study, incremental reductions in the PA pressures in the monitored arm were associated with both reduction in the frequency of HFH and improvements in health-related quality of life among patients with both preserved (HFpEF) and reduced ejection fraction (HFrEF).3,4 Additionally, hemodynamic-guided HF management in the subset of HFrEF patients treated with guideline-directed medical therapy (GDMT) was associated with a strong trend toward improved survival compared to traditional clinical management.4,7 Consistent benefit is demonstrated in several retrospective studies from the CHAMPION Trial.10-13 as well as extensive analysis of “real-world� experience.6,14 and in Medicare claims data managed in a commercial setting.5,15 Whether the benefits of PA pressure guided therapy can be extended to a broader pool of patients with milder (NYHA class II) or more severe (NYHA class IV) HF or to those without recent hospitalization for HF but with elevation in natriuretic peptide levels remains unclear. Remotely uploaded PA pressure information from the control group will be blocked from investigator review. [...]other than medication changes resulting from information from RHC procedures, control group subjects will not have pressure-based medication changes over time and should be managed instead according to routine practice as informed by published clinical guidelines. Thresholds for NT-proBNP/BNP corrected for BMI using a 4% reduction per BMI unit over 25 kg/m2 Subjects ≥18 y of age able and willing to provide informed consent Chest circumference of 15) at implant RHC, a history of noncompliance, or any condition that would preclude CardioMEMS PA Sensor implantation Table I Inclusion and exclusion criteria PA pressure goals PA diastolic: 8-20 mm Hg PA mean: 10-25 mm Hg PA systolic: 15-35 mm Hg Optimization phas

Extent of Methionine Limitation in Peak-, Early-, and Mid-Lactation Dairy Cows

Five multiparous, ruminally and duodenally cannulated Holstein cows were assigned to 5 × 5 Latin squares at wk 2 (experiment 1), wk 11 to 13 (experiment 2), and wk 17 to 19 postpartum (experiment 3) to determine extent of Met limitation. Treatments were duodenally infused and consisted of 10 g/d of l-Lys plus 0, 3.5, 7.0, 10.5, or 16.0 g/d of dl-Met in experiments 1 and 2 and 8 g/d of l-Lys plus 0, 5, 10, 15, or 20 g/d of dl-Met in experiment 3. Calculated Lys contributions to total AA (TAA) in duodenal digesta for control treatments were 8.6, 7.5, and 9.0% for experiments 1, 2, and 3, respectively. Methionine contributions to TAA for the 5 infusion treatments were 1.9, 2.1, 2.2, 2.4, and 2.7% for experiment 1; 2.1, 2.3, 2.4, 2.5, and 2.7% for experiment 2; and 1.8, 2.0, 2.2, 2.4, and 2.5% for experiment 3, respectively. Milk protein yield increased linearly in experiments 1 and 2, indicating that Met contribution to TAA in duodenal digesta for maximal milk protein synthesis exceeded 2.7 for early-lactation cows. In experiment 2, a quadratic relationship was found between level of infused Met and milk protein content, with the response reaching a plateau when 12.2 g of Met was infused, corresponding with a Met contribution to TAA in duodenal digesta of 2.4%. In experiment 3, milk protein content increased quadratically, but milk yield declined linearly with increasing levels of infused Met; hence, milk protein yield was unaffected by treatment. The calculated plateau point of the milk protein content response curve was determined to be 12.4 g of infused Met, which corresponds to a Met contribution to TAA in duodenal digesta of 2.3%. Experiment 3 results indicate that the required level of Met in duodenal digesta for maximizing milk protein yield is lower than that required for maximizing milk protein content