Efficacy and muscle safety assessment of fukutin-related protein gene therapy.

Limb-girdle muscular dystrophy type R9 (LGMDR9) is a muscle-wasting disease that begins in the hip and shoulder regions of the body. This disease is caused by mutations in fukutin-related protein (FKRP), a glycosyltransferase critical for maintaining muscle cell integrity. Here we investigated potential gene therapies for LGMDR9 containing an FKRP expression construct with untranslated region (UTR) modifications.

Quantification of Branched-Chain Amino Acids in Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Branched-chain amino acids (BCAA), including valine, alloisoleucine, isoleucine, and leucine, play significant roles in a number of metabolic pathways in the body. Deficiency in branched-chain ketoacid dehydrogenase complex, an enzyme required for metabolism of those amino acids, will lead to elevation and accumulation of BCAA and ketoacids in bodily fluids. This results in maple syrup urine disease (MSUD), a condition estimated to affect 1 in 100,000-300,000 births.

The Impact of COVID-19 on Laboratory Test Utilization at a Pediatric Medical Center.

Background: The epidemiology and clinical manifestation of coronavirus disease 2019 (COVID-19) in the pediatric population is different from the adult population. The purpose of this study is to identify effects of the COVID-19 pandemic on laboratory test utilization in a pediatric hospital.

Methods: We performed retrospective analysis on test utilization data from Ann & Robert H.

A rapid LC-MS/MS assay for detection and monitoring of underivatized branched-chain amino acids in maple syrup urine disease.

Introduction: Quantitation of the isomeric branched-chain amino acids (BCAA; valine, alloisoleucine, isoleucine, leucine) is a challenging task that typically requires derivatization steps or long runtimes if a traditional chromatographic method involving a ninhydrin ion pairing reagent is used.

Objectives: To develop and perform clinical validation of a rapid, LC-MS/MS-based targeted metabolomics assay for detection and monitoring of underivatized BCAA in human plasma.

Methods: Various columns and modes of chromatography were tested.

Comparison between the kinematics for kangaroo rat hopping on a solid versus sand surface.

In their natural habitats, animals move on a variety of substrates, ranging from solid surfaces to those that yield and flow (e.g. sand).

Elastic energy storage across speeds during steady-state hopping of desert kangaroo rats (Dipodomys deserti).

Small bipedal hoppers, including kangaroo rats, are not thought to benefit from substantial elastic energy storage and return during hopping. However, recent species-specific material properties research suggests that, despite relative thickness, the ankle extensor tendons of these small hoppers are considerably more compliant than had been assumed. With faster locomotor speeds demanding higher forces, a lower tendon stiffness suggests greater tendon deformation and thus a greater potential for elastic energy storage and return with increasing speed.

Plantar flexor muscles of kangaroo rats (Dipodomys deserti) shorten at a velocity to produce optimal power during jumping.

The musculotendon work contributions across all joints during jumping by kangaroo rats are not well understood. Namely, measures of external joint work do not provide information on the contributions from individual muscles or in-series elastic structures. In this study, we examined the functional roles of a major ankle extensor muscle, the lateral gastrocnemius (LG), and a major knee extensor muscle, the vastus lateralis (VL), through in vivo sonomicrometry and electromyography techniques, during vertical jumping by kangaroo rats.

Myosin cross-bridge kinetics slow at longer muscle lengths during isometric contractions in intact soleus from mice.

Muscle contraction results from force-generating cross-bridge interactions between myosin and actin. Cross-bridge cycling kinetics underlie fundamental contractile properties, such as active force production and energy utilization. Factors that influence cross-bridge kinetics at the molecular level propagate through the sarcomeres, cells and tissue to modulate whole-muscle function.

Estimation of the force-velocity properties of individual muscles from measurement of the combined plantarflexor properties.

The force-velocity (-) properties of isolated muscles or muscle fibers have been well studied in humans and other animals. However, determining properties of individual muscles remains a challenge because muscles usually function within a synergistic group. Modeling has been used to estimate the properties of an individual muscle from the experimental measurement of the muscle group properties.

Specimen Temperature Detection on a Clinical Laboratory Pre-Analytic Automation Track: Implications for Direct-from-Track Total Laboratory Automation (TLA) Systems.

Clinical laboratory regulations require temperature monitoring of facilities, reagent and specimen storage, as well as temperature-dependent equipment. Real-time specimen temperature detection has not yet been integrated into total laboratory automation (TLA) solutions. An infrared (IR) pyrometer was paired with a complementary metal oxide semiconductor (CMOS) laser sensor and connected to an embedded networked personal computer (PC) to create a modular temperature detection unit for closed, moving clinical laboratory specimens.

Yank: the time derivative of force is an important biomechanical variable in sensorimotor systems.

The derivative of force with respect to time does not have a standard term in physics. As a consequence, the quantity has been given a variety of names, the most closely related being 'rate of force development'. The lack of a proper name has made it difficult to understand how different structures and processes within the sensorimotor system respond to and shape the dynamics of force generation, which is critical for survival in many species.

Automation of chromatographic peak review and order to result data transfer in a clinical mass spectrometry laboratory.

Introduction: Mass spectrometry-based assays have increasingly been implemented in clinical laboratories for their multiplexing capacity and high specificity and sensitivity. However, these methods are often associated with labor-intensive and error-prone data-related workflows, due to the volume of data generated that is often manually reviewed and resulted. We aimed to establish a system within our clinical mass spectrometry laboratory to facilitate data 'flow' from electronic medical record order to result and to automate processes for chromatogram peak review.

Tendons from kangaroo rats are exceptionally strong and tough.

Tendons must be able to withstand the forces generated by muscles and not fail. Accordingly, a previous comparative analysis across species has shown that tendon strength (i.e.

The Contributions of Individual Muscle-Tendon Units to the Plantarflexor Group Force-Length Properties.

The combined force-length (F-L) properties of a muscle group acting synergistically at a joint are determined by several aspects of the F-L properties of the individual musculotendon units. Namely, misalignment of the optimal lengths of the individual muscles will affect the group F-L properties. This misalignment, which we named [Formula: see text], arises from the properties of the muscles (i.

Jumping mechanics of desert kangaroo rats.

Kangaroo rats are small bipedal desert rodents that use erratic vertical jumps to escape predator strikes. In this study we examined how individual hind limb joints of desert kangaroo rats () power vertical jumps across a range of heights. We hypothesized that increases in net work would be equally divided across hind limb joints with increases in jump height.

Effect of Subject-Specific Vertebral Position and Head and Neck Size on Calculation of Spine Musculoskeletal Moments.

Spine musculoskeletal models used to estimate loads and displacements require many simplifying assumptions. We examined how assumptions about subject size and vertebral positions can affect the model outcomes. Head and neck models were developed to represent 30 subjects (15 males and 15 females) in neutral posture and in forward head postures adopted while using tablet computers.

Concordance analysis of paired cancer antigen (CA) 15-3 and 27.29 testing.

Purpose: Cancer antigens (CA) 15-3 and 27.29 are used in the clinical management of many breast cancer patients. Given that immunoassays for CA 15-3 and CA 27.

Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i.

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i.

Multi-Center Benchmark Study Reveals Significant Variation in Thyroid Testing in United States.

Background: Studies show that a significant portion of laboratory testing is unnecessary. Thyroid tests are some of the most commonly ordered laboratory tests, yet little is known about practice patterns for laboratory testing for thyroid disease. The objective of this study was to collect data on practice patterns for thyroid testing in the United States.

Sexually dimorphic skeletal muscle and cardiac dysfunction in a mouse model of limb girdle muscular dystrophy 2i.

The fukutin-related protein P448L mutant mouse replicates many pathologies common to limb girdle muscular dystrophy 2i (LGMD2i) and is a potentially strong candidate for relevant drug screening studies. Because striated muscle function remains relatively uncharacterized in this mouse, we sought to identify metabolic, functional and histological metrics of exercise and cardiac performance. This was accomplished by quantifying voluntary exercise on running wheels, forced exercise on respiratory treadmills and cardiac output with echocardiography and isoproterenol stress tests.

Trendelenburg-Like Gait, Instability and Altered Step Patterns in a Mouse Model for Limb Girdle Muscular Dystrophy 2i.

Limb-girdle muscular dystrophy type 2i (LGMD2i) affects thousands of lives with shortened life expectancy mainly due to cardiac and respiratory problems and difficulty with ambulation significantly compromising quality of life. Limited studies have noted impaired gait in patients and animal models of different muscular dystrophies, but not in animal models of LGMD2i. Our goal, therefore, was to quantify gait metrics in the fukutin-related protein P448L mutant (P448L) mouse, a recently developed model for LGMD2i.

Gravitational demand on the neck musculature during tablet computer use.

Tablet computer use requires substantial head and neck flexion, which is a risk factor for neck pain. The goal of this study was to evaluate the biomechanics of the head-neck system during seated tablet computer use under a variety of conditions. A physiologically relevant variable, gravitational demand (the ratio of gravitational moment due to the weight of the head to maximal muscle moment capacity), was estimated using a musculoskeletal model incorporating subject-specific size and intervertebral postures from radiographs.

Temperature fluctuations in the lower limbs of young and elderly individuals during activities of daily living.

Age-related deficiencies in thermoregulation diminish the capacity to defend against heat loss under conditions often encountered during activities of daily living (ADL). A potential consequence of these deficiencies is that elderly individuals could have colder lower limbs, which would exacerbate the age-related decline in plantarflexor contractile properties and compromise recovery from a tripping incident. Moreover, a common self-perception among the elderly is that their limbs are cold.