Exploring the associations between skeletal muscle echogenicity and physical function in aging adults: A systematic review with meta-analyses.

BACKGROUND: Assessment and quantification of skeletal muscle within the aging population is vital for diagnosis, treatment, and injury/disease prevention. The clinical availability of assessing muscle quality through diagnostic ultrasound presents an opportunity to be utilized as a screening tool for function-limiting diseases. However, relationships between muscle echogenicity and clinical functional assessments require authoritative analysis. Thus, we aimed to (a) synthesize the literature to assess the relationships between skeletal muscle echogenicity and physical function in older (≥60 years) adults, (b) perform pooled analyses of relationships between skeletal muscle echogenicity and physical function, and (c) perform sub-analyses to determine between-muscle relationships. METHODS: CINAHL, Embase, MEDLINE, PubMed, and Web of Science databases were systematically searched to identify articles relating skeletal muscle echogenicity to physical function in older adults. Risk-of-bias assessments were conducted along with funnel plot examination. Meta-analyses with and without sub-analyses for individual muscles were performed utilizing Fisher's Z transformation for the most common measures of physical function. Fisher's Z was back-transformed to Pearson's r for interpretation. RESULTS: Fifty-one articles (n = 5095, female = ∼2759, male = ∼2301, 72.5 ± 5.8 years, mean ± SD (1 study did not provide sex descriptors)) were extracted for review, with previously unpublished data obtained from the authors of 13 studies. The rectus femoris (n = 34) and isometric knee extension strength (n = 22) were the most accessed muscle and physical qualities, respectively. The relationship between quadriceps echogenicity and knee extensor strength was moderate (n = 2924, r = -0.36 (95% confidence interval: -0.38 to -0.32), p < 0.001), with all other meta-analyses (grip strength, walking speed, sit-to-stand, timed up-and-go) resulting in slightly weaker correlations (r = -0.34 to -0.23, all p < 0.001). Sub-analyses determined minimal differences in predictive ability between muscle groups, although combining muscles (e.g., rectus femoris + vastus lateralis) often resulted in stronger correlations with maximal strength. CONCLUSION: While correlations were modest, the affordable, portable, and noninvasive ultrasonic assessment of muscle quality was a consistent predictor of physical function in older adults. Minimal between-muscle differences suggest that echogenicity estimates of muscle quality are systemic. Therefore, practitioners may be able to scan a single muscle to estimate full-body skeletal muscle quality/composition, while researchers should consider combining multiple muscles to strengthen the model.

Lung and Heart Biology of the Dp16 Mouse Model of down Syndrome: Implications for Studying Cardiopulmonary Disease.

(1) Background: We sought to investigate the baseline lung and heart biology of the Dp16 mouse model of Down syndrome (DS) as a prelude to the investigation of recurrent respiratory tract infection. (2) Methods: In controls vs. Dp16 mice, we compared peripheral blood cell and plasma analytes. We examined baseline gene expression in lungs and hearts for key parameters related to susceptibility of lung infection. We investigated lung and heart protein expression and performed lung morphometry. Finally, and for the first time each in a model of DS, we performed pulmonary function testing and a hemodynamic assessment of cardiac function. (3) Results: Dp16 mice circulate unique blood plasma cytokines and chemokines. Dp16 mouse lungs over-express the mRNA of triplicated genes, but not necessarily corresponding proteins. We found a sex-specific decrease in the protein expression of interferon α receptors, yet an increased signal transducer and activator of transcription (STAT)-3 and phospho-STAT3. Platelet-activating factor receptor protein was not elevated in Dp16 mice. The lungs of Dp16 mice showed increased stiffness and mean linear intercept and contained bronchus-associated lymphoid tissue. The heart ventricles of Dp16 mice displayed hypotonicity. Finally, Dp16 mice required more ketamine to achieve an anesthetized state. (4) Conclusions: The Dp16 mouse model of DS displays key aspects of lung heart biology akin to people with DS. As such, it has the potential to be an extremely valuable model of recurrent severe respiratory tract infection in DS.

Ultrasound measures of muscle morphology in people with multiple sclerosis are associated with muscle performance and functional mobility.

BACKGROUND: Neurologically-based muscle weakness is a common symptom in people with multiple sclerosis MS (MS), who may also exhibit muscle morphology changes and intrinsic muscle dysfunction. Diagnostic ultrasound (sonography) is a non-invasive, inexpensive, and clinically feasible method to measure muscle morphology. The purpose of this study was to investigate possible asymmetries in lower limb muscle morphology and performance in people with MS, and to assess the relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. METHODS: This cross-sectional study was conducted at the Washington, DC Veterans Affairs Medical Center. The study participants were 29 Veterans with MS (52% female, 79% African-American, 48.6 ± 11.2 years old, Mean Expanded Disability Status Scale: 3.6 ± 1.4) who completed seated knee extension isokinetic strength and power tests, functional assessments (Timed 25-Foot Walk - T25FW, 5-Times Sit-to-Stand - 5STS), and quantitative B-mode ultrasound image acquisition of the rectus femoris muscle to derive morphology measures (thickness and echogenicity). The limb with weaker knee extension strength was identified as the more-involved limb. Differences between the more and less-involved limb were quantified using a t-test for all muscle morphology and muscle performance measures. Relationships between muscle morphology and patient characteristics, muscle performance, and functional mobility were evaluated using bivariate and multivariate analyses. RESULTS: The rectus femoris thickness from the more-involved limb was lower (p<0.001) than that of the less-involved limb, whereas echogenicity was not different between the two limbs (p=0.147). Rectus femoris thickness of the more-involved limb was directly related to age (r=-0.63, p<0.001), muscle strength (r=0.53, p=0.003) and power (r=0.53, p=0.003), and gait speed (r=0.42, p=0.024); whereas its echogenicity was positively associated only with muscle strength (r=-0.46, p=0.013) and power (r=-0.50, p=0.006). Together rectus femoris thickness and echogenicity of the more involved limb explained 44% and 48% of the variance in muscle strength and power, respectively (p<0.001). CONCLUSION: This study supports the ability of sonography to measure muscle morphology in people with MS, identify asymmetries, and quantify associations with important clinical correlates. Compared with more invasive and costly alternatives, sonography is a clinically feasible, relatively low-cost tool that can be used to assess muscle morphology in people with MS. Further research is warranted to determine the potential clinical utility of sonographic measures of muscle morphology in evaluating changes due to disease progression or therapeutic interventions in this population.

Metalloproteinases and their inhibitors are associated with pulmonary arterial stiffness and ventricular function in pediatric pulmonary hypertension.

Disturbed balance between matrix metalloproteinases (MMPs) and their respective tissue inhibitors (TIMPs) is a well-recognized pathophysiological component of pulmonary arterial hypertension (PAH). Both classes of proteinases have been associated with clinical outcomes as well as with specific pathological features of ventricular dysfunction and pulmonary arterial remodeling. The purpose of this study was to evaluate the circulating levels of MMPs and TIMPs in children with PAH undergoing the same-day cardiac magnetic resonance imaging (MRI) and right heart catheterization. Children with PAH (n = 21) underwent a same-day catheterization, comprehensive cardiac MRI evaluation, and blood sample collection for proteomic analysis. Correlative analysis was performed between protein levels and 1) standard PAH indices from catheterization, 2) cardiac MRI hemodynamics, and 3) pulmonary arterial stiffness. MMP-8 was significantly associated with the right ventricular end-diastolic volume (R = 0.45, P = 0.04). MMP-9 levels were significantly associated with stroke volume (R = -0.49, P = 0.03) and pulmonary vascular resistance (R = 0.49, P = 0.03). MMP-9 was further associated with main pulmonary arterial stiffness evaluated by relative area change (R = -0.79, P < 0.01).TIMP-2 and TIMP-4 levels were further associated with the right pulmonary artery pulse wave velocity (R = 0.51, P = 0.03) and backward compression wave (R = 0.52, P = 0.02), respectively. MMPs and TIMPs warrant further clinically prognostic evaluation in conjunction with the conventional cardiac MRI hemodynamic indices.NEW & NOTEWORTHY Metalloproteinases have been associated with clinical outcomes in pulmonary hypertension and with specific pathological features of ventricular dysfunction and pulmonary arterial remodeling. In this study, we demonstrated that plasma circulating levels of metalloproteinases and their inhibitors are associated with standard cardiac MRI hemodynamic indices and with the markers of proximal pulmonary arterial stiffness. Particularly, MMP-9 and TIMP-2 were associated with several different markers of pulmonary arterial stiffness. These findings suggest the interplay between the extracellular matrix (ECM) remodeling and overall hemodynamic status in children with PAH might be assessed using the peripheral circulating MMP and TIMP levels.

Dynamic compression of human and ovine meniscal tissue compared with a potential thermoplastic elastomer hydrogel replacement.

Understanding how human meniscal tissue responds to loading regimes mimetic of daily life as well as how it compares to larger animal models is critical in the development of a functionally accurate synthetic surrogate. Seven human and eight ovine cadaveric meniscal specimens were regionally sectioned into cylinders 5 mm in diameter and 3 mm thick along with 10 polystyrene-b-polyethylene oxide block copolymer-based thermoplastic elastomer (TPE) hydrogels. Samples were compressed to 12% strain at 1 Hz for 5000 cycles, unloaded for 24 h, and then retested. No differences were found within each group between test one and test two. Human and ovine tissue exhibited no regional dependency (p < 0.05). Human samples relaxed quicker than ovine tissue or the TPE hydrogel with modulus values at cycle 50 not significantly different from cycle 5000. Ovine menisci were found to be similar to human menisci in relaxation profile but had significantly higher modulus values (3.44 MPa instantaneous and 0.61 MPa after 5000 cycles compared with 1.97 and 0.11 MPa found for human tissue) and significantly different power law fit coefficients. The TPE hydrogel had an initial modulus of 0.58 MPa and experienced less than a 20% total relaxation over the 5000. Significant differences in the magnitude of compressive modulus between human and ovine menisci were observed, however the relaxation profiles were similar. Although statistically different than the native tissues, modulus values of the TPE hydrogel material were similar to those of the human and ovine menisci, making it a material worth further investigation for use as a synthetic replacement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2722-2728, 2017.