Mendelian randomization provides evidence for a causal effect of serum insulin-like growth factor family concentration on risk of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is one of the most common persistent arrhythmias among adult cardiovascular diseases. It is important to identify potential risk factors for AF. Members of the insulin-like growth factor (IGF) family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases, and previous population-based studies indicate associations between IGF family members and AF. However, the causal effects of IGF family members in AF have not been evaluated. AIM: In the current study two-sample Mendelian Randomization (MR) was used to assess genetic relationships between IGF family members and AF. METHODS: MR was performed based on genome-wide association study (GWAS) datasets, and concentration levels of 14 IGF family members were retrieved. An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations. A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects. Two-sample MR packages were used to perform MR analysis in R. MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods were used. RESULTS: In two-sample MR assessments there were lower levels of circulating IGF binding protein 3 in both WM [odds ratio (OR) 0.964, 95% confidence interval (CI) 0.940-0.960, P = 0.006] and IVW (OR 0.968, 95%CI: 0.947-0.987, P = 0.001) analyses. Higher serum levels of IGF2 receptor were associated with AF (OR 1.045, 95%CI: 1.016-1.076, P = 0.039). In reverse MR analysis conducted to investigate casual effects, elevated levels of circulating CYR61 were associated with AF (OR 1.060, 95%CI: 1.005-1.119, P = 0.031). CONCLUSION: The results of the present study provide novel insights into the pathogenesis of AF, and the implications of serum IGF family member concentrations when assessing the risk of AF. The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF. Further observational and experimental studies are critically needed.

Slow Dynamics in a Quasi-Two-Dimensional Binary Complex Plasma.

Slow dynamics in an amorphous quasi-two-dimensional complex plasma, comprised of microparticles of two different sizes, was studied experimentally. The motion of individual particles was observed using video microscopy, and the self-part of the intermediate scattering function as well as the mean-squared particle displacement was calculated. The long-time structural relaxation reveals the characteristic behavior near the glass transition. Our results suggest that binary complex plasmas can be an excellent model system to study slow dynamics in classical supercooled fluids.

The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in Partial Bladder Outlet Obstruction in Rats.

BACKGROUND/AIMS: Antimuscarinic agents can delay the progression of bladder dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship between muscarinic receptor activity and the bladder extracellular matrix (ECM) remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was established to explore the variation in bladder wall ECM proteins under PBOO conditions with antimuscarinic agent administration. METHODS: Rats were randomly divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red staining was used to examine the smooth muscle and collagen content of bladder samples. Gene microarray and RT-PCR were performed to survey the expression of ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive results were further evaluated by immunohistochemistry. RESULTS: Picrosirius red staining showed that smooth muscle volume significantly increased in the PBOO and PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene microarray and RT-PCR revealed that none of the collagen subtypes exhibited significant changes after PBOO establishment and tolterodine administration. However, matrix metalloproteinases (MMPs) increased significantly in the PBOO plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the expression of non-collagen ECM proteins and ECM receptors. CONCLUSIONS: Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly via MMPs, and regulated the expression of ECM proteins and receptors.

Efficacy and safety of barbed suture in minimally invasive radical prostatectomy: A systematic review and meta-analysis.

As one of the earliest surgeries applying knotless barbed suture, the minimally invasive radical prostatectomy (MIRP) was reported to have various effects on the patients and the surgeons. This study reviewed the available evidence about the efficacy and safety of barbed sutures in MIRP. We searched ClinicalTrials.gov, Cochrane Register of Clinical Studies, PubMed, and Embase to identify randomized controlled trials (RCTs) and cohort studies addressing the application of barbed sutures and conventional sutures in MIRP (until August 2016). Quality assessment was performed according to Cochrane recommendations. The data were analyzed using Review Manager (Version 5.3), and sensitivity analysis was performed by sequentially omitting each study. A total of 12 studies, including three RCTs (low to moderate risk of bias, 211 patients) and nine cohort studies (low to moderate risk of bias, 698 patients), fulfilled the study criteria. The pooling of trials did not show statistical difference. Pooling data of cohort studies showed that suture time [mean difference (MD) = -8.52, 95% confidence interval (CI) = -12.60 to -4.43, p < 0.0001] and length of hospital stay (MD = -0.96, 95% CI = -1.80 to -0.11, p = 0.03) were significantly shorter in the barbed group. Results of continence rate varied according to different studies. Subgroup analysis by type of MIRP suggested that patients who underwent barbed suture during robot-assisted surgeries had a shorter hospital stay (MD = -1.13, 95% CI = -1.82 to -0.45, p = 0.001). During the laparoscopic surgery, patients in the barbed suture group had fewer postoperative complications [odds ratio = 0.29, 95% CI = 0.08-0.98, p = 0.05). However, more evidence is needed to validate this state-of-the-art technology.

Risk factors for recurrence in female urethral diverticulectomy: a retrospective study of 66 patients.

PURPOSE: We aimed to report surgical outcomes in female urethral diverticula and to investigate the risk factors for diverticula recurrence. METHODS: A total of 66 patients underwent urethral diverticulectomies from January 2009 to October 2015 at out institution. Patient and diverticula characteristics were collected. Mean follow-up was 28.8 months (range 4-85 months). Recurrence was defined as requiring a repeat diverticulectomy. RESULTS: Mean age was 44.9 years. Mean duration of symptoms was 28.1 months. Seven cases had previous urethral surgeries. Mean diverticula size was 2.8 cm. Main clinical symptoms included dribbling (n = 41), vaginal mass (n = 41), dysuria (n = 33), frequency/urgency (n = 29), infection (n = 24), stress urinary incontinence (SUI) (n = 20) and dyspareunia (n = 8). 10 cases had proximal diverticula, 10 cases had multiple diverticula, and 35 cases had horseshoe/circumferential diverticula. Postoperatively, the recurrence rate was 19.7 %. Preoperative SUI disappeared in 14 cases, and de novo SUI was developed in six cases. One case developed urethral stricture, and no cases reported urinary fistula. Among 60 cases with pathological results, neoplastic change was seen in one case (1.7 %). Besides, atypical hyperplasia (n = 2) and metaplasia (n = 3) were observed. Univariate analysis suggested that age, duration, follow-up, diverticula size and diverticula shape were not associated with surgical outcomes. Patients with multiple diverticula (p = 0.032), proximal diverticula (p = 0.042) and those with previous urethral procedures (p = 0.004) were at risk of recurrent diverticula confirmed by multivariate logistic regression analysis. CONCLUSIONS: The surgical outcomes of urethral diverticulectomies were acceptable. Multiple diverticula, proximal diverticula and previous urethral surgery were three independent risk factors for recurrent diverticula.