Cardiac Denervation for Arrhythmia Treatment with Transesophageal Ultrasonic Strategy in Canine Models

Stellate ganglion (SG) modification has been investigated for arrhythmia treatment. In this study, transesophageal SG imaging and intervention were explored using a homemade 30F integrated focused ultrasonic catheter in healthy mongrel canines in vivo. Anatomic details of SGs were ultrasonically imaged and evaluated. SG had a heterogeneous echoic structure and characteristic profiles sketched by hyper-echoic outlines in an ultrasonogram. Left SGs in the experimental group were successfully ablated through the esophagus under ultrasonic guidance provided by the catheter itself. Two weeks after the ablation, the QT and QTc of the experimental group decreased compared with those of the sham group and at baseline (both p values < 0.001). Histologic examination revealed that left SGs were destroyed. No major complications were observed. This approach may be further explored as a method for ganglia remodeling evaluation and as a strategy of ganglia modification for arrhythmia and for other diseases.     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.