Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.     

Accuracy of atrial fibrillation detection by an insertable cardiac monitor in patients undergoing catheter ablation: Results of the BioVAD study

BackgroundInsertable cardiac monitors (ICMs) are increasingly used to evaluate the atrial fibrillation (AF) burden after catheter ablation of AF. BioMonitor III (BM3) is an ICM with a long sensing vector, which enhances sensing capabilities. The AF detection algorithm of the BM3 is based on R–R interval variability.ObjectiveTo evaluate the performance of the AF detection algorithm of BM3 in patients before and after catheter ablation of AF using simultaneous Holter recordings.MethodsIn this prospective study, we enrolled patients scheduled for catheter ablation of paroxysmal or persistent AF. After BM3 implantation, patients had a 4 days Holter registration before and 3 months after ablation. All true AF episodes ≥2 min on the Holter were annotated and matched with BM3 detected AF detections.ResultsThirty‐one patients were enrolled (mean age 60 ± 8, 74% male, 68% paroxysmal AF). Fifty‐six Holter registrations were performed in 30 patients. Twelve patients demonstrated at least one true AF episode with a total AF duration of 570 h. The AF burden accuracy of BM3 before catheter ablation was 99.6%, with a duration sensitivity of 98.6% and a duration specificity of 99.9%. The AF burden accuracy of BM3 after catheter ablation was 99.8%, with a duration sensitivity of 90.2% and a duration specificity of 99.9%. Overall, the AF burden detected on the Holter and BM3 demonstrated a high Pearson correlation coefficient of 0.996.ConclusionBM3 accurately detects AF burden in patients before and after catheter ablation of AF.     

Rasch-based scoring offered more precision in differentiating patient groups in measuring upper limb function

ObjectiveTo compare the discriminatory ability of Rasch-based and summative scoring in the context of assessing upper limb function of patients with stroke.Study Design and SettingData were from a cohort study of 497 adults with stroke undergoing physiotherapy. Upper limb function was assessed at admission and discharge using the upper limb subscale of the Motor Assessment Scale (UL-MAS). Rasch analysis was used to transform raw UL-MAS scores into interval measures. A relative precision (RP) index was used to differentiate patients by discharge destination.ResultsThe analysis confirmed the unidimensional structure of UL-MAS at both admission and discharge and demonstrated the adequate fit of the items. The RP index favored the Rasch-based scoring over the summative scoring in differentiating between the two patient groups, with significant gains in precision at admission (15%) and discharge (11%). When examining patients in the upper or lower quartile of UL-MAS, the gains in precision were statistically significant in favor of the Rasch-based scoring, with 20% precision at admission and 19% precision at discharge.ConclusionRasch-based scoring was more precise in differentiating patient groups by discharge destination than the summative scoring used to measure upper limb function, especially at the extreme range of the scale.