Pathogenic variants in COL6A3 cause Ullrich-like congenital muscular dystrophy in young Labrador Retriever dogs

The collagen VI-related muscular dystrophies in people include a broad spectrum of diseases ranging from the severe Ullrich congenital muscular dystrophy to the mild Bethlem myopathy. Clinical features are attributable to both muscle and connective tissue and include progressive muscle weakness and respiratory failure, hyperlaxity of distal joints, and progressive contracture of large joints. Here we describe two different COL6A3 pathogenic variants in Labrador Retriever dogs that result in autosomal recessive or autosomal dominant congenital myopathies with hyperlaxity of distal joints and joint contracture, similar to the condition in people

161. The Potential Role of Extensor Muscle Fatigue in the Onset of Intervertebral Disc Degeneration: A Novel In Vivo Model

BACKGROUND CONTEXT: Occupation is strongly correlated to low back pain (LBP). Specific occupational activities associated with low back pain include poor posture, whole body vibration, and repetitive lifting. These activities have a common link: they result in fatigue of the primary spinal extensor musculature. This fatigue may lead to increased intervertebral loading - a stimulus for disc degeneration. If true, this association could provide a vital connection between detrimental physical activities and LBP. However, the link between muscle fatigue and increased load across the disc space has never been quantified in vivo. PURPOSE: The purpose of this study was to develop and test a wireless multi-axial force-sensing implant and large animal model of primary extensor muscle fatigue. Combined, these tools allow measurement of in vivo spinal forces during muscle fatigue to quantify changes in spine loading

P95. In Vivo Loads in the Cervical Spine: A Preliminary Investigation Using a Force-Sensing Implant

BACKGROUND CONTEXT: It is estimated that up to 80% of the general population will experience at least one significant bout of low back pain in their lifetime. The leading known cause of low back pain is degenerative disc disease (DDD). Many established risk factors for low back pain and DDD are mechanical in nature and are often related to occupational activities, such as poor posture and frequent/heavy lifting. Altered mechanical loading in the spine has been shown to be a potential stimulus for disc degeneration. However, a link between occupational/environmental factors and intervertebral loading has never been demonstrated in vivo. We hypothesize that intervertebral loading is highly dependent on muscle activation and recruitment. These relationships are significant because they provide a potential connection between everyday activities and low back pain. PURPOSE: The purpose of this study was to use a novel force-sensing interbody implant to measure in vivo loads in the disc space of the goat cervical spine in real time and analyze their dependence on activity, posture, rate of motion, and whole body compensation

262. Direct Measure of Cervical Interbody Forces in Vivo: Load Reversal after Plating

BACKGROUND CONTEXT: Biomechanics play an important role in spine fusion, but the in vivo biomechanics of the cervical spine are not well characterized and the in vivo biomechanics after spinal arthrodesis have never been studied. Load sharing facilitates fusion, but overloading of interbody implants can lead to subsidence and failure. In vitro studies have demonstrated that anterior plating significantly alters mechanical loading in the cervical spine. The instantaneous axis of rotation is shifted anteriorly and loading is reversed relative to an uninstrumented spine; the interbody space is compressed during extension and unloaded during flexion. However, this has never been tested in vivo and the magnitude of loads in the instrumented and uninstrumented cervical spine are unknown. PURPOSE:The purpose of this studywas to use a novel force-sensing implant to directly measure interbody loading in the cervical spine in real time in vivo in a large animal model following instrumented or uninstrumented arthrodesis. STUDY DESIGN/SETTING: In vivo biomechanical loading following anterior cervical discectomy and fusion (ACDF) in goats

BIOGRAPHIES

Austin in 2011. While an undergraduate student in Austin, he worked for two-and-a-half years at the Applie

161. The Potential Role of Extensor Muscle Fatigue in the Onset of Intervertebral Disc Degeneration: A Novel In Vivo Model

BACKGROUND CONTEXT: Occupation is strongly correlated to low back pain (LBP). Specific occupational activities associated with low back pain include poor posture, whole body vibration, and repetitive lifting. These activities have a common link: they result in fatigue of the primary spinal extensor musculature. This fatigue may lead to increased intervertebral loading - a stimulus for disc degeneration. If true, this association could provide a vital connection between detrimental physical activities and LBP. However, the link between muscle fatigue and increased load across the disc space has never been quantified in vivo. PURPOSE: The purpose of this study was to develop and test a wireless multi-axial force-sensing implant and large animal model of primary extensor muscle fatigue. Combined, these tools allow measurement of in vivo spinal forces during muscle fatigue to quantify changes in spine loading

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder:Association to overlapping traits in ADHD and autism

AbstractAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.</jats:p

Assessing the risk of human-to-wildlife pathogen transmission for conservation and public health.

The SARS-CoV-2 pandemic has led to increased concern over transmission of pathogens from humans to animals, and its potential to threaten conservation and public health. To assess this threat, we reviewed published evidence of human-to-wildlife transmission events, with a focus on how such events could threaten animal and human health. We identified 97 verified examples, involving a wide range of pathogens; however, reported hosts were mostly non-human primates or large, long-lived captive animals. Relatively few documented examples resulted in morbidity and mortality, and very few led to maintenance of a human pathogen in a new reservoir or subsequent "secondary spillover" back into humans. We discuss limitations in the literature surrounding these phenomena, including strong evidence of sampling bias towards non-human primates and human-proximate mammals and the possibility of systematic bias against reporting human parasites in wildlife, both of which limit our ability to assess the risk of human-to-wildlife pathogen transmission. We outline how researchers can collect experimental and observational evidence that will expand our capacity for risk assessment for human-to-wildlife pathogen transmission