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New Findings: What is the central question of this study?We previously demonstrated that quercetin transiently preserved respiratory function in dystrophin‐deficient mice. To gain lasting therapeutic benefits, we tested quercetin in combination with nicotinamide riboside, lisinopril and prednisolone in the D2‐mdx model.What is the main finding and its importance?We demonstrated that these quercetin‐based cocktails did not preserve respiratory or diaphragmatic function or reduce histological damage after 7 months of treatment starting at 4 months of age. Duchenne muscular dystrophy is characterized by the absence of dystrophin protein and causes muscle weakness and muscle injury, culminating in respiratory failure and cardiomyopathy. Quercetin transiently improved respiratory function but failed to maintain long‐term therapeutic benefits in mdx mice. In this study, we combined quercetin with nicotinamide riboside (NR), lisinopril and prednisolone to assess the efficacy of quercetin‐based cocktails. We hypothesized that quercetin, NR and lisinopril independently would improve respiratory function and decrease diaphragmatic injury and when combined would have additive effects. To address this hypothesis, in vivo respiratory function, in vitro diaphragmatic function and histological injury were assessed in DBA (healthy), D2‐mdx (dystrophic) and D2‐mdx mice treated with combinations of quercetin, NR and lisinopril from 4 to 11 months of age. Respiratory function, assessed using whole‐body plethysmography, was largely similar between healthy and dystrophin‐deficient mice. Diaphragm specific tension was decreased by ∼50% in dystrophic mice compared with healthy mice (P < 0.05), but fatigue resistance was similar between groups. Contractile area was decreased by ∼10% (P < 0.05) and fibrotic area increased from 3.5% in healthy diaphragms to 27% (P < 0.05) in dystrophic diaphragms. Contrary to expectations, these functional and histological parameters of disease were not offset by any intervention. These data suggest that quercetin, NR and lisinopril, independently and in combination, did not prevent diaphragmatic injury or preserve respiratory function. [ABSTRACT FROM AUTHOR]

The present ASTM procedure for field measurement of the noise reduction between spaces is time consuming and costly because it requires numerous measurements in order to compute the noise isolation class (NIC), particularly when separate measurements must be made at multiple microphone positions to obtain adequate spatial averaging. The purpose of the present investigation is to explore the relationships between NIC values based on 13-oct band data and more easily obtained ratings of isolation based on either octave band data or on A-weighted or C-weighted sound level data. A large number of curves of 13-oct band noise reduction versns frequency were calculated from data on transmission loss of partitions, assumed room geometry, assumed values for the source sound power spectrum, and assumed values for the sound absorption in the source and receive rooms. For each of these 13-oct band noise reduction curves, the following quantities were calculated and compared: NIC rating, Ia rating (13-oct band data), Ia rating (octave band data), the A-weighted sound level difference, and the difference between the C-weighted level in the source room and the A-weighted level in the receive room. [ABSTRACT FROM AUTHOR]

Measurements of insertion loss and interior masking noise were conducted using a representative sampling of 23 1972-1973 automobiles. One-third octave-band insertion losses were determined for each car for different orientations with respect to the sound source. One-third octave-band interior masking noise levels were determined from tape recordings made during preselected portions of a test drive. An estimate of the sound level and frequency required of a warning device to be 'heard' by the driver inside an automobile is given. [ABSTRACT FROM AUTHOR]

Measurements have been made to determine the directivity and the sound power spectra of four electronic sirens and nine electromechanical sirens. Also investigated briefly were destructive interference effects (1) between a pair of electronic sirens, and (2) between the direct signal from a siren and the signal reflected from the pavement. A discussion is given of the data and the implications of the results regarding the efficacy of these sirens as warning devices on emergency vehicles. [ABSTRACT FROM AUTHOR]

Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy. We showed previously that quercetin (Q) partially protected dystrophic limb muscles from disease-related injury. As quercetin activates PGC-1α through Sirtuin-1, an NAD + -dependent deacetylase, the depleted NAD + in dystrophic skeletal muscle may limit quercetin efficacy; hence, supplementation with the NAD + donor, nicotinamide riboside (NR), may facilitate quercetin efficacy. Lisinopril (Lis) protects skeletal muscle and improves cardiac function in dystrophin-deficient mice; therefore, it was included in this study to evaluate the effects of lisinopril used with quercetin and NR. Our purpose was to determine the extent to which Q, NR, and Lis decreased dystrophic injury. We hypothesized that Q, NR, or Lis alone would improve muscle function and decrease histological injury and when used in combination would have additive effects. Muscle function of 11-mo-old DBA (healthy), D2-mdx (dystrophin-deficient), and D2-mdx mice was assessed after treatment with Q, NR, and/or Lis for 7 mo. To mimic typical pharmacology of patients with Duchenne muscular dystrophy, a group was treated with prednisolone (Pred) in combination with Q, NR, and Lis. At 11 mo of age, dystrophin deficiency decreased specific tension and tetanic force in the soleus and extensor digitorum longus muscles and was not corrected by any treatment. Dystrophic muscle was more sensitive to contraction-induced injury, which was partially offset in the QNRLisPred group, whereas fatigue was similar between all groups. Treatments did not decrease histological damage. These data suggest that treatment with Q, NR, Lis, and Pred failed to adequately maintain dystrophic limb muscle function or decrease histological damage. NEW & NOTEWORTHY Despite a compelling rationale and previous evidence to the contrary in short-term investigations, quercetin, nicotinamide riboside, or Lisinopril, alone or in combination, failed to restore muscle function or decrease histological injury in dystrophic limb muscle from D2-mdx mice after long-term administration. Importantly, we also found that in the D2-mdx model, an emerging and relatively understudied model of Duchenne muscular dystrophy dystrophin deficiency caused profound muscle dysfunction and histopathology in skeletal muscle.

Objectives: The current laboratory study quantified blood oxidative stress to woodsmoke exposure., Methods: Participants inhaled woodsmoke during three randomized crossover exercise trials (Clean Air [0 μg/m], Low Exposure [250 μg/m], and High Exposure [500 μg/m], Woodsmoke [particulate matter less than 2.5 μm, PM2.5]). Trolox equivalent antioxidant capacity (TEAC), uric acid (UA), 8-isoprostanes (8-ISO), lipid hydroperoxides (LOOH), protein carbonyls (PC), nitrotyrosine (3-NT), 8-isoprostane, and myeloperoxidase (MPO) were quantified in Pre, immediately Post, and 1- (1Hr) hour post blood samples., Results: UA decreased following Low Exposure, while plasma TEAC levels increased Post and 1Hr. LOOH levels decreased 1Hr Post (High Exposure), while 8-Iso increased following both smoke trials. PC and MPO were unchanged following all trials, while 3-NT increased over Clean Air., Conclusion: Blood oxidative stress occurred largely independent of PM2.5 concentrations. Future studies should employ longer duration smoke and exercise combined with physiologic parameters.

New Findings: What is the central question of this study? The central question of this study is to understand whether dietary quercetin enrichment attenuates physiologic, histological, and biochemical indices of cardiac pathology. What is the main finding and its importance? Novel findings from this investigation, in comparison to prior published studies, suggest that mouse strain-dependent cardiac outcomes in performance and remodelling exist. Unlike Mdx/Utrn -/+ mice, mdx mice receiving lifelong quercetin treatment did not exhibit improvements cardiac function. Similar to prior work in Mdx/Utrn -/+ mice, histological evidence of remodelling suggests that quercetin consumption may have benefited hearts of mdx mice. Positive outcomes may be related to indirect markers that suggest improved mitochondrial wellbeing and to selected indices of inflammation that were lower in hearts from quercetin-fed mice. Duchenne muscular dystrophy causes a decline in cardiac health, resulting in premature mortality. As a potential countermeasure, quercetin is a polyphenol possessing inherent anti-inflammatory and antioxidant effects that activate proliferator-activated γ coactivator 1α (PGC-1α), increasing the abundance of mitochondrial biogenesis proteins. We investigated the extent to which lifelong 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in mdx mice. Dystrophic animals were fed a quercetin-enriched or control diet for 12 months, while control C57 mice were fed a control diet. Cardiac function was assessed via 7 T magnetic resonance imaging at 2, 10 and 14 months. At 14 months, hearts were harvested for histology and Western blotting. The results indicated an mdx strain-dependent decline in cardiac performance at 14 months and that dietary quercetin enrichment did not attenuate functional losses. In contrast, histological analyses provided evidence that quercetin feeding was associated with decreased fibronectin and indirect damage indices (Haematoxylin and Eosin) compared with untreated mdx mice. Dietary quercetin enrichment increased cardiac protein abundance of PGC-1α, cytochrome c, electron transport chain complexes I-V, citrate synthase, superoxide dismutase 2 and glutathione peroxidase (GPX) versus untreated mdx mice. The protein abundance of the inflammatory markers nuclear factor-κB, phosphorylated nuclear factor kappa beta (P-NFκB) and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (P-IKBα) was decreased by quercetin compared with untreated mdx mice, while preserving nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha( IKBα) compared with mdx mice. Furthermore, quercetin decreased transforming growth factor-β1, cyclooxygenase-2 (COX2) and macrophage-restricted F4/80 protein (F4/80) versus untreated mdx mice. The data suggest that long-term quercetin enrichment does not impact physiological parameters of cardiac function but improves indices of mitochondrial biogenesis and antioxidant enzymes, facilitates dystrophin-associated glycoprotein complex (DGC) assembly and decreases inflammation in dystrophic hearts., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

Duchenne Muscular Dystrophy (DMD) is associated with progressive cardiac pathology; however, the SIRT1/PGC1-α activator quercetin may cardioprotect dystrophic hearts. We tested the extent to which long-term 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in Mdx/Utrn +/- mice. At 2 mo, Mdx/Utrn +/- mice were fed quercetin-enriched (Mdx/Utrn +/- -Q) or control diet (Mdx/Utrn +/- ) for 8 mo. Control C57BL/10 (C57) animals were fed a control diet for 10 mo. Cardiac function was quantified by MRI at 2 and 10 mo. Spontaneous physical activity was quantified during the last week of treatment. At 10 mo hearts were excised for histological and biochemical analysis. Quercetin feeding improved various physiological indexes of cardiac function in diseased animals. Mdx/Utrn +/- -Q also engaged in more high-intensity physical activity than controls. Histological analyses of heart tissues revealed higher expression and colocalization of utrophin and α-sarcoglycan. Lower abundance of fibronectin, cardiac damage (Hematoxylin Eosin-Y), and MMP9 were observed in quercetin-fed vs. control Mdx/Utrn +/- mice. Quercetin evoked higher protein abundance of PGC-1α, cytochrome c, ETC complexes I-V, citrate synthase, SOD2, and GPX compared with control-fed Mdx/Utrn +/- Quercetin decreased abundance of inflammatory markers including NFκB, TGF-β1, and F4/80 compared with Mdx/Utrn +/- ; however, P-NFκB, P-IKBα, IKBα, CD64, and COX2 were similar between groups. Dietary quercetin enrichment improves cardiac function in aged Mdx/Utrn +/- mice and increases mitochondrial protein content and dystrophin glycoprotein complex formation. Histological analyses indicate a marked attenuation in pathological cardiac remodeling and indicate that long-term quercetin consumption benefits the dystrophic heart., New & Noteworthy: The current investigation provides first-time evidence that quercetin provides physiological cardioprotection against dystrophic pathology and is associated with improved spontaneous physical activity. Secondary findings suggest that quercetin-dependent outcomes are in part due to PGC-1α pathway activation., (Copyright © 2017 the American Physiological Society.)