Browsing by Subject "muscle"

Now showing 1 - 5 of 5
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    Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants
    (Future Medicine, 2019-09-27) Sadhasivam, Senthilkumar; Henker, Richard A.; Brandom, Barbara W.; McAuliffe, John J.; Anesthesia, School of Medicine
    Aim: Identify variants in RYR1, CACNA1S and STAC3, and predict malignant hyperthermia (MH) pathogenicity using Bayesian statistics in individuals clinically treated as MH susceptible (MHS). Materials & methods: Whole exome sequencing including RYR1, CACNA1S and STAC3 performed on 64 subjects with: MHS; suspected MH event or first-degree relative; and MH negative. Variant pathogenicity was estimated using in silico analysis, allele frequency and prior data to calculate Bayesian posterior probabilities. Results: Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Conclusion: Bayesian method provides new approach to predict MH pathogenicity of genetic variants.
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    Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways
    (Frontiers, 2016) Barreto, Rafael; Mandili, Giorgia; Witzmann, Frank A.; Novelli, Francesco; Zimmers, Teresa A.; Bonetto, Andrea; Department of Surgery, IU School of Medicine
    Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0.05; -1.5 ≥ fold change ≥ +1.5). Comparative analysis isolated 240 proteins that were modulated in common, with a large majority (218) that were down-regulated in both experimental settings. Interestingly, metabolic (47.08%) and structural (21.25%) proteins were the most represented. Pathway analysis revealed mitochondrial dysfunctions in both experimental conditions, also consistent with reduced expression of mediators of mitochondrial fusion (OPA-1, mitofusin-2), fission (DRP-1) and biogenesis (Cytochrome C, PGC-1α). Alterations of oxidative phosphorylation within the TCA cycle, fatty acid metabolism, and Ca(2+) signaling were also detected. Overall, the proteomic signature in the presence of both chemotherapy and cancer suggests the activation of mechanisms associated with movement disorders, necrosis, muscle cell death, muscle weakness and muscle damage. Conversely, this is consistent with the inhibition of pathways that regulate nucleotide and fatty acid metabolism, synthesis of ATP, muscle and heart function, as well as ROS scavenging. Interestingly, strong up-regulation of pro-inflammatory acute-phase proteins and a more coordinated modulation of mitochondrial and lipidic metabolisms were observed in the muscle of the C26 hosts that were different from the Folfiri-treated animals. In conclusion, our results suggest that both cancer and chemotherapy contribute to muscle loss by activating common signaling pathways. These data support the undertaking of combination strategies that aim to both counteract tumor growth and reduce chemotherapy side effects.
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    Forelimb muscle architecture and myosin isoform composition in the groundhog (Marmota monax)
    (2015) Rupert, Joseph E.; Rose, Jacob A.; Organ, Jason M.; Butcher, Michael T.; Department of Anatomy & Cell Biology, IU School of Medicine
    Scratch-digging mammals are commonly described as having large, powerful forelimb muscles for applying high force to excavate earth, yet studies quantifying the architectural properties of the musculature are largely unavailable. To further test hypotheses about traits that represent specializations for scratch-digging, we quantified muscle architectural properties and myosin expression in the forelimb of the groundhog (Marmota monax), a digger that constructs semi-complex burrows. Architectural properties measured were muscle moment arm, muscle mass (MM), belly length (ML), fascicle length (lF), pennation angle and physiological cross-sectional area (PCSA), and these metrics were used to estimate maximum isometric force, joint torque and power. Myosin heavy chain (MHC) isoform composition was determined in selected forelimb muscles by SDS-PAGE and densitometry analysis. Groundhogs have large limb retractors and elbow extensors that are capable of applying moderately high torque at the shoulder and elbow joints, respectively. Most of these muscles (e.g. latissimus dorsi and pectoralis superficialis) have high lF/ML ratios, indicating substantial shortening ability and moderate power. The unipennate triceps brachii long head has the largest PCSA and is capable of the highest joint torque at both the shoulder and elbow joints. The carpal and digital flexors show greater pennation and shorter fascicle lengths than the limb retractors and elbow extensors, resulting in higher PCSA/MM ratios and force production capacity. Moreover, the digital flexors have the capacity for both appreciable fascicle shortening and force production, indicating high muscle work potential. Overall, the forelimb musculature of the groundhog is capable of relatively low sustained force and power, and these properties are consistent with the findings of a predominant expression of the MHC-2A isoform. Aside from the apparent modifications to the digital flexors, the collective muscle properties observed are consistent with its behavioral classification as a less-specialized burrower and these may be more representative of traits common to numerous rodents with burrowing habits or mammals with some fossorial ability.
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    The Intramuscular Course of the Greater Occipital Nerve: Novel Findings with Potential Implications for Operative Interventions and Occipital Neuralgia
    (2014-10) Tubbs, R. Shane; Watanabe, Koichi; Loukas, Marios; Cohen-Gadol, Aaron A.; Department of Neurology, IU School of Medicine
    Background: A better understanding of the etiologies of occipital neuralgia would help the clinician treat patients with this debilitating condition. Since few studies have examined the muscular course of the greater occipital nerve (GON), this study was performed. Methods: Thirty adult cadaveric sides underwent dissection of the posterior occiput with special attention to the intramuscular course of the GON. Nerves were typed based on their muscular course. Results: The GON traveled through the trapezius (type I; n = 5, 16.7%) or its aponeurosis (type II; n = 15, 83.3%) to become subcutaneous. Variations in the subtrapezius muscular course were found in 10 (33%) sides. In two (6.7%) sides, the GON traveled through the lower edge of the inferior capitis oblique muscle (subtype a). On five (16.7%) sides, the GON coursed through a tendinous band of the semispinalis capitis, not through its muscular fibers (subtype b). On three (10%) sides the GON bypassed the semispinalis capitis muscle to travel between its most medial fibers and the nuchal ligament (subtype c). For subtypes, eight were type II courses (through the aponeurosis of the trapezius), and two were type I courses (through the trapezius muscle). The authors identified two type IIa courses, four type IIb courses, and two type IIc courses. Type I courses included one type Ib and one type Ic courses. Conclusions: Variations in the muscular course of the GON were common. Future studies correlating these findings with the anatomy in patients with occipital neuralgia may elucidate nerve courses vulnerable to nerve compression. This enhanced classification scheme describes the morphology in this region and allows more specific communications about GON variations.
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    ULTRASOUND IMAGING AS A DIAGNOSTIC TOOL FOR MUSCLE, TENDON AND FASCIA PATHOLOGIES: AN EMERGING PHYSICAL THERAPY PRACTICE
    (Office of the Vice Chancellor for Research, 2012-04-13) White, Danielle; Bird, Chelsea; Bayliss, Amy J.; Loghmani, Terry M.
    Objective: Ultrasonography (US) is a front-runner for diagnostic imaging in musculoskeletal pathologies associated with muscle, tendon and fascia. The objective of this review was to systematically identify and summarize the literature on current trends of diagnostic ultrasonography in physical therapy. In addition, we expect to establish the merit, validity, and reliabil-ity of diagnostic ultrasonography. Method: A literature search was conducted using: PubMed, ProQuest, Science Direct, Thompson, EMBASE, OVID, CINAHL, and MEDLINE data-bases. Keywords that were used: diagnostic ultrasound, musculoskeletal conditions, rehabilitation, physical therapy. Findings: The current applications for US involving muscle, includes identifying superficial muscles, such as transversus abdominis and multifidus, to provide biofeedback for muscle re-education and measuring cross-sectional area to predict force generation. For tendons, US provides high-resolution images of inflammation, blood flow, and tendon width that assists in diagnosing pathologies such as Achilles tendonitis. US yields clear visualization of fascial thickness and is used to help determine potential eti-ology, confirm clinical diagnosis, and gauge the efficacy of intervention in plantar fasciitis. Research shows that the overall accuracy of US in musculoskeletal medi-cine is significantly similar to the gold standard of diagnostic imaging- MRI. Compared to MRI, US is safer, more convenient, less expensive, non-invasive, and dynamic. Limiting aspects of US include being restricted to su-perficial structures and a lack of minimum clinically important difference val-ues (MCID). Conclusion: Overall, there is a convincing body of evidence supporting the use of US in diagnosis and assessment of muscle, tendon and fascia conditions. Taking into consideration the surplus of clinical applications and advantages over other imaging tools, US is becoming a promising primary instrument for diagnosing and assessing musculoskeletal disorders in physi-cal rehabilitation. The results from this literature review will be used to sup-port the design of clinical trials investigating the effectiveness of manual therapy techniques.