Bruxism in awake dogs as a clinical sign of forebrain disease: 4 cases

BACKGROUND: Bruxism is a repetitive masticatory muscle activity characterized by clenching or grinding of the teeth, or by bracing or thrusting of the mandible, or both. OBJECTIVES: To investigate whether bruxism in awake dogs could be associated with brain lesions. ANIMALS: Four dogs with episodic bruxism in the awake state. METHODS: Observational retrospective single‐center case series. Inclusion criteria were dogs examined between 2010 and 2021 with episodic bruxism as a presenting complaint or observed during the examination or hospitalization, complete medical records and magnetic resonance imaging or computed tomography of the brain. Bruxism during epileptic seizures as oroalimentary automatism was an exclusion criterion. RESULTS: Four dogs met the inclusion criteria. Two dogs had bruxism while awake as a presenting complaint, whereas in the remaining 2 it was a clinical finding. All dogs had neuroanatomical localization consistent with a forebrain lesion, with diencephalic involvement in 3/4. The diagnostic evaluation was consistent with neoplasia (n = 2) and meningoencephalitis of unknown origin (n = 2), in 1 case accompanied by corpus callosum abnormality affecting the forebrain, in 3 dogs advanced imaging findings were suggestive of increased intracranial pressure. All dogs were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the presence of bruxism in the awake state associated with other neurological deficits might indicate a forebrain lesion

Exploring the role of central nervous system myelination in circuit function and behaviour

Activity-mediated myelination, the adjustment of myelin morphology in response to neuronal activity, has been proposed as a novel mechanism of central nervous system (CNS) plasticity. As a key regulator of conduction velocity, adaptations in myelin structure have the potential to exert spatiotemporal control over action potentials across neurons of a given circuit, in turn influencing circuit function and behaviour. Despite a breadth of evidence supporting this hypothesis, a definitive conclusion has been hindered by the technical difficulties of assessing circuit activity in parallel with myelin morphology and behaviour in vivo. Using larval zebrafish as a model, this study investigated the effect of disrupting the normal program of CNS myelination on the development of locomotor behaviour. CRISPR/Cas9 mutagenesis of Myelin Regulatory Factor (Myrf) gene, encoding for a transcription factor vital for CNS myelination, was used to create a CNS specific model of hypomyelination. Larvae from Myrf heterozygous in-crosses were then tested across a suite of behavioural assays, allowing the measurement of detailed kinematic parameters during spontaneous and stimulus-driven responses. Myrf homozygous mutants displayed a 66% reduction in the number of myelinated axons in the spinal cord along with reduced gene expression of myelin basic protein (Mbp). Unexpectedly, heterozygous animals exhibited precocious myelination of small caliber axons, resulting in a 53% increase in the number of myelinated axons. This finding was associated with a subtle upregulation of Mbp gene expression. Subsequent behavioural analysis revealed that Myrf homozygous mutants demonstrated a significant delay in the latency to perform acoustic startle responses. Interestingly, both homozygous and heterozygous mutants exhibited an increase in the frequency of high velocity swim bouts performed during spontaneous swimming, driven by subtle adjustments in tail kinematics. The findings of this study support a role for myelination in the control of action potential timing across defined circuits of the CNS and suggest that a balance of myelination is important for the function of more complex circuits such as those controlling swim speed. Future work, using in vivo electrophysiology and functional imaging, will interrogate how neuronal activity is altered in the circuits underlying these behaviours. Together, these findings will advance our understanding of the role that CNS myelination plays in circuit function and behaviour

Water for Texas: Applicant Capacity Assessment Tool for the Economically Distressed Areas Program

This report contains recommendations, analysis, and an assessment tool for the Economically Distressed Areas program administered by the Texas Water Development Board. The purpose of the assessment tool, known as the Applicant Capacity Assessment Tool (ACAT), was to reduce the number of water infrastructure projects running over-budget and over-schedule

CNS Hypomyelination Disrupts Axonal Conduction and Behavior in Larval Zebrafish

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, because of their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behavior. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias toward reorientation behavior instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high-frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function. SIGNIFICANCE STATEMENT Myelination of CNS axons is essential for their health and function, and it is now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behavior and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, because of their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behavior of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular, and circuit level analyses of myelination using this model

Complications associated with cerebrospinal fluid collection in dogs.

BackgroundThis study aimed to identify complications associated with cerebrospinal fluid (CSF) collection in dogs.MethodsThis was a prospective, observational multicentre study using data collected from 102 dogs undergoing CSF collection for the investigation of neurological disease. CSF was collected from the cerebellomedullary cistern (CMC), lumbar subarachnoid space (LSAS) or both sites. Pre-, intra- and postprocedural data were collected. Descriptive statistics were performed to outline complications associated with CSF collection.ResultsCSF sampling was attempted on 108 occasions, and CSF was acquired on 100 occasions (92.6%). Collection from the CMC was more likely to be successful than that from the LSAS. No dogs exhibited neurologic deterioration following CSF collection. There was no significant difference between pre- and post-CSF collection short-form Glasgow composite measure pain scores in ambulatory dogs (p = 0.13).LimitationsThe scarcity of complications limited the ability to quantify the incidence of some potential complications reported elsewhere.ConclusionsOur results may be used to inform clinicians and owners that CSF sampling is associated with a low frequency of complications when performed by trained personnel

Idiopathic and structural episodic nonintentional head tremor in dogs: 100 cases (2004-2022).

BackgroundAlthough idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT).Hypothesis/objectivesDescribe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT.AnimalsOne hundred dogs with IEHT (n = 71) or SEHT (n = 29).MethodsRetrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022.ResultsLesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P Conclusions and clinical importancePresence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education