Implementation of 2D Running Gait Analysis in Orthopedic Physical Therapy Clinics.

Background: Despite 2D motion analysis deemed valid and reliable in assessing gait deviations in runners, current use of video-based motion analysis among orthopedic physical therapists is not prevalent. Purpose/Hypothesis: To investigate clinician-perceived effectiveness, adherence, and barriers to using a 2D running gait analysis protocol for patients with running-related injuries. Study Design: Survey. Methods: Thirty outpatient physical therapy clinics were contacted to assess interest in participation. Participating therapists were trained on 2D running gait analysis protocol and given a running gait checklist. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to assess the implementation process by collecting a baseline survey at the beginning of the study, effectiveness and implementation surveys at two months, and a maintenance survey at six months. Results: Twelve of the 15 responding clinics met eligibility criteria, giving a Reach rate of 80%. Twelve clinicians from 10 different clinics participated, giving an Adoption rate of 83%. For Effectiveness, the majority of clinicians valued having a checklist, and reported the protocol was easy to conduct, the methodology was reasonable and appropriate, and patients saw the benefits of using the protocol. Assessing Implementation, 92% performed all steps of the protocol on all appropriate runners. Average time spent conducting the protocol was 32 minutes. With respect to Maintenance, 50% reported continuing to use the protocol, while 50% answered they were not to continue use. Conclusion: Clinicians expressed a perceived benefit of implementing a running gait analysis protocol with common themes of ease of use, being a useful adjunct to evaluating a patient, and increased satisfaction with treating injured runners. Potential barriers for not using the protocol included not having an appropriate clinic setup, time constraints, and not having adequate caseload. Level of Evidence: 3b.

Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice.

RATIONALE: Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task. OBJECTIVES: Here, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans. METHOD: Using male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment. RESULTS: Amphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance. CONCLUSION: These data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context.

Fate mapping Nkx2.1-lineage cells in the mouse telencephalon.

The homeodomain transcription factor Nkx2.1 is expressed in the pallidal (subcortical) telencephalon, including the medial ganglionic eminence (MGE) and preoptic area. Studies have shown that Nkx2.1 is required for normal patterning of the MGE and for the specification of the parvalbumin (PV)- and somatostatin (SST)-expressing cortical interneurons. To define the contribution of Nkx2.1 lineages to neurons in the mature telencephalon, we have generated transgenic mice carrying the genomic integration of a modified bacterial artificial chromosome (BAC) in which the second exon of Nkx2.1 is replaced by the Cre recombinase. Analysis of these mice has found that they express the Cre recombinase and Cre reporters within Nkx2.1-expressing domains of the brain, thyroid, pituitary, and lung. Telencephalic expression of reporters begins at about embryonic day 10.5. Expression both of Cre and of recombination-based Cre reporters is weaker within the dorsalmost region of the MGE than in other Nkx2.1-expressing regions. In this paper, we present fate-mapping data on Nkx2.1-lineage neurons throughout the telencephalon, including the cerebral cortex, amygdala, olfactory bulb, striatum, globus pallidus, septum, and nucleus basalis.

Tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists.

Novel tricyclic imidazoline antagonists of the adenosine A1 receptor are described. For key compounds, the selectivity level over other adenosine receptor subtypes is examined along with their in vivo effects in a rat diuresis model. Compound 14, the (R)-isomer of 7,8-dihydro-8-ethyl-2-(4-bicyclo[2.2.2]octan-1-ol)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one, is a particularly potent adenosine A1 receptor antagonist with good selectivity over the other three adenosine receptor subtypes: A1 (human) Ki=22 nM; A2A (human) Ki=4400 nM; A2B (human) Ki=580 nM; A3 (human) Ki>or=10,000 nM. Imidazoline 14 is a competitive adenosine A1 receptor antagonist with a pA2 value of 8.88 and is highly soluble in water (>100 mg/mL). In addition, it has an oral bioavailability of 84% and an oral half-life of 3.8 h in rats. When orally administered in a rat diuresis model, compound 14 promoted sodium excretion (ED50=0.01 mg/kg). This level of efficacy is comparable to that of BG9928, a selective adenosine A1 receptor antagonist that is currently in clinical trials as a treatment for congestive heart failure. Additional modifications to 14 also showed that the bridgehead hydroxyl group could be replaced with a propionic acid (compound 36) without a significant loss in binding affinity or in vivo activity.