Publications by authors named "C G Wilson"

Rationale: Synthetic cannabinoid receptor agonists (SCRAs) are found in illicit smoking products, such as "K2" or "Spice." Convulsions are commonly reported adverse effects of SCRAs but are poorly understood.

Objectives: We determined convulsant effects of SCRAs AB-PINACA, and 5F-ADB-PINACA in adult male NIH Swiss mice, and then determined if convulsant effects of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 elicited seizure-like effects using EEG.

Methods: Mice were administered SCRAs or pentylenetetrazole (PTZ) and placed in observation chambers where convulsant effects were scored. The capacity of the CB1R antagonist rimonabant, the benzodiazepine diazepam, or the non-specific CYP450 inhibitor 1-aminobenzotriazole (1-ABT) to attenuate convulsant effects was determined. Other mice were prepared with EEG headmounts to ascertain whether observed convulsions occurred concurrently with seizure-like effects by assessing root-mean-square (RMS) power, high amplitude EEG spike analysis, and videography.

Results: Mice receiving AB-PINACA or 5F-ADB-PINACA exhibited dose-dependent convulsant effects that were blocked by 10 mg/kg rimonabant pretreatment but not by pretreatment with 10 mg/kg diazepam; these convulsant effects were not altered in the presence of 100 mg/kg 1-ABT. Repeated administration of 10 mg/kg AB-PINACA and 3 mg/kg 5F-ADB-PINACA produced partial tolerance to convulsant effects but did not lead to cross-tolerance to PTZ-induced convulsions. In EEG studies, convulsant doses of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 did not produce seizures concomitantly with convulsions.

Conclusions: These data extend previous findings of convulsant effects of SCRAs and suggest that convulsant effects of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 are CB1R-mediated but are not associated with electroencephalographic seizures. These results further suggest that benzodiazepines may not effectively treat convulsions elicited by SCRA use in humans.

Plasma membrane calcium ATPase 1 (PMCA1, Atp2b1) is emerging as a key contributor to cardiac physiology, involved in calcium handling and myocardial signalling. In addition, genome wide association studies have associated PMCA1 in several areas of cardiovascular disease including hypertension and myocardial infarction. Here, we investigated the role of PMCA1 in basal cardiac function and heart rhythm stability. Cardiac structure, heart rhythm and arrhythmia susceptibility were assessed in a cardiomyocyte-specific PMCA1 deletion (PMCA1) mouse model. PMCA1 mice developed abnormal heart rhythms related to ventricular repolarisation dysfunction and displayed an increased susceptibility to ventricular arrhythmias. We further assessed the levels of cardiac ion channels using qPCR and found a downregulation of the voltage-dependent potassium channels, K4.2, with a corresponding reduction in the transient outward potassium current which underlies ventricular repolarisation in the murine heart. The changes in heart rhythm were found to occur in the absence of any structural cardiomyopathy. To further assess the molecular changes occurring in PMCA1 hearts, we performed proteomic analysis. Functional characterisation of differentially expressed proteins suggested changes in pathways related to metabolism, protein-binding, and pathways associated cardiac function including β-adrenergic signalling. Together, these data suggest an important role for PMCA1 in basal cardiac function in relation to heart rhythm control, with reduced cardiac PMCA1 expression resulting in an increased risk of arrhythmia development.

Objectives: The primary aim of this study was to better understand North Carolina providers' specific substance use disorder (SUD) and opioid use disorder treatment practices and buprenorphine prescribing. Furthermore, this study aimed to provide novel information regarding US South and rural providers' opioid use disorder treatment behaviors and perceptions of patient experience at community pharmacies.

Methods: An online survey consisting of closed-ended and open-ended questions was used. Surveys were delivered to healthcare providers' e-mails and self-administered. Surveys were administered through an online survey platform.

Results: In total, 332 healthcare providers, who were eligible to be X-waivered to prescribe buprenorphine, completed the online survey. Survey participants reported not having their X-waiver to prescribe buprenorphine or actively prescribing buprenorphine. The majority of participants were uncertain of potential barriers to filling buprenorphine prescriptions. Providers treating a mix of rural and urban patients reported being less likely to screen for SUDs. Although there were no rurality differences in SUD screening, providers who treat mostly rural patients reported a lack of SUD treatment options in their area.

Conclusions: Early detection of SUDs can help prevent negative health outcomes for patients. Regardless of patient rurality, providers should screen for SUDs and familiarize themselves with the patient's experience when filling a buprenorphine prescription, along with possible barriers. Furthermore, providers should incorporate questions about their patient's ability to receive buprenorphine to help ensure that patients are receiving proper and necessary treatment.

Background The prevalence of chronic obstructive pulmonary disease (COPD) in women is fast approaching that in men, and women experience greater symptom burden. Although sex differences in emphysema have been reported, differences in airways have not been systematically characterized. Purpose To evaluate whether structural differences in airways may underlie some of the sex differences in COPD prevalence and clinical outcomes. Materials and Methods In a secondary analyses of a multicenter study of never-, current-, and former-smokers enrolled from January 2008 to June 2011 and followed up longitudinally until November 2020, airway disease on CT images was quantified using seven metrics: airway wall thickness, wall area percent, and square root of the wall thickness of a hypothetical airway with internal perimeter of 10 mm (referred to as Pi10) for airway wall; and lumen diameter, airway volume, total airway count, and airway fractal dimension for airway lumen. Least-squares mean values for each airway metric were calculated and adjusted for age, height, ethnicity, body mass index, pack-years of smoking, current smoking status, total lung capacity, display field of view, and scanner type. In ever-smokers, associations were tested between each airway metric and postbronchodilator forced expiratory volume in 1 second (FEV)-to-forced vital capacity (FVC) ratio, modified Medical Research Council dyspnea scale, St George's Respiratory Questionnaire score, and 6-minute walk distance. Multivariable Cox proportional hazards models were created to evaluate the sex-specific association between each airway metric and mortality. Results In never-smokers ( = 420), men had thicker airway walls than women as quantified on CT images for segmental airway wall area percentage (least-squares mean, 47.68 ± 0.61 [standard error] vs 45.78 ± 0.55; difference, -1.90; = .02), whereas airway lumen dimensions were lower in women than men after accounting for height and total lung capacity (segmental lumen diameter, 8.05 mm ± 0.14 vs 9.05 mm ± 0.16; difference, -1.00 mm; < .001). In ever-smokers ( = 9363), men had greater segmental airway wall area percentage (least-squares mean, 52.19 ± 0.16 vs 48.89 ± 0.18; difference, -3.30; < .001), whereas women had narrower segmental lumen diameter (7.80 mm ± 0.05 vs 8.69 mm ± 0.04; difference, -0.89; < .001). A unit change in each of the airway metrics (higher wall or lower lumen measure) resulted in lower FEV-to-FVC ratio, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all < .01). Conclusion Airway lumen sizes quantified at chest CT were smaller in women than in men after accounting for height and lung size, and these lower baseline values in women conferred lower reserves against respiratory morbidity and mortality for equivalent changes compared with men. © RSNA, 2022

Introduction: Safe aging in place (SAIP) is when an older adult can successfully and comfortably remain in their home despite increasing barriers, including falls. Various physical, medical, psychological, and psychosocial factors may individually or cumulatively impact an older adult's ability to safely age in place. Physiotherapists should assess not only items traditionally considered within their scope of practice but should select efficient and effective outcome measures to quantify other domains of health. A comprehensive geriatric assessment (CGA) is an evidence-based clinical assessment which identifies medical, psychosocial, and functional limitations of an older person. The CGA is useful to dictate individualized exercise/intervention prescription to address identified areas of increased risk.

Purpose And Importance To Practice: The purpose of this Masterclass is to describe key screening, assessments, and interventions to facilitate SAIP and to provide overviews of currently available programming and care delivery models applicable to physiotherapist practice. There are a wide variety of outcome measures and interventions that vary in depth, validity, and reliability. Measures selected for inclusion in this Masterclass were chosen based upon their clinical utility with respect to time and resource constraints and ease of administration during a comprehensive assessment for SAIP in community-dwelling older adults. Measures recommended for assessing physical function were the Short Physical Performance Battery, the Timed-Up-and-Go, the 30 second chair rise test, and the Four Test Balance Scale. Additionally, measures from the heath domain (e.g., Functional Comorbidity Index) and the environmental domain (e.g., Home FAST) are recommended. Relative to interventions, the Otago Exercise Program, motivational interviewing, home modifications, and leveraging technology are recommended. Partnerships with community-facing organizations facilitate utilization of resources for sustainable SAIP. The Home-based Older Person Upstreaming Prevention Physical Therapy (HOP-UP-PT) program is one approach led by physiotherapists framed in the screening, assessments, and interventions discussed in this Masterclass with strong scientific grounding.

Conclusion: Programs integrating both community and healthcare approaches have the strongest evidence for their utility; however, implementation for these preventative approaches are lagging behind the increased need due to the substantial population growth of those over 65 years.