Catheter Ablation of Idiopathic Premature Ventricular Contractions and Ventricular Tachycardias Originating from the Vicinity of Endocardial and Epicardial Mitral Annulus

Background

Several previous reports have revealed that idiopathic ventricular arrhythmias (VAs), including premature ventricular contractions (PVCs) and ventricular tachycardias (IVTs), can originate from endocardial mitral annulus (ENDO MA). However, these data are limited to ENDO MA VAs, and little is known about the electrocardiographic (ECG) characteristics and the efficacy of radiofrequency catheter ablation (RFCA) via the coronary venous system for the VAs arising from the epicardial MA (EPI MA).

Methodology/Principal Findings

Characteristics of body surface electrocardiogram and electrophysiologic recordings were analyzed in 21 patients with symptomatic PVCs/IVTs originating from the vicinity of MA. Among 597 patients with PVCs/IVTs, the incidence of VAs originating from the ENDO and EPI MA was 3.52% (21 cases). Eleven (52%) from the ENDO MA, and 10 (48%) from the EPI MA. There were different characteristics of ECG of PVCs/VT originating from the ENDO and EPI MA. The prolonged pseudodelta wave time and intrinsicoid deflection time in lead V2 and the precordial maximum deflection index reliably differentiated EPI MA VAs from ENDO MA VAs with high sensitivity and specificity. Successful RFCA in 18 patients could be achieved (85.7% acute procedural success).

Conclusions/Significance

ECG characteristics of PVCs/VTs originating from the different portions of the MA are different, and can help regionalize the origin of these arrhythmias. RFCA within the coronary venous system was relatively effective and safe for the PVCs/IVTs and should be seen as an alternative approach, when the MA PVCs/IVTs could not be eliminated by RFCA from the endocardium.     

Diabetic Patients Could Do As Well as Non-Diabetic Patients without Inflammation on Peritoneal Dialysis

Background

Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.

Methods

Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.

Results

Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.

Conclusion

Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.     

Landscape-Scale Disturbances Modified Bird Community Dynamics in Successional Forest Environment

Ecosystem-based forest management strives to develop silvicultural practices that best emulate natural disturbances such as wildfire to conserve biodiversity representative of natural forest ecosystems. Yet, current logging practices alter forest structure and reduce the proportion of old-growth forest and, consequently, can exert long-term effects on the dynamics of forest biota. The stand- and landscape-scale factors driving bird community dynamics in post-disturbance environment remain poorly understood. In this study, we examined bird community dynamics along successional gradients in boreal ecosystems originating from fire and logging in landscapes dominated by old-growth forest. We tested if bird species richness and community compositions in clear-cutting stands became comparable to those in natural stands after 70 years, and identified the relative contributions of stand- and landscape-scale forest attributes in bird community dynamics. Based on records of bird occurrences at 185 field sites in natural and clearcutting stands, we demonstrate that (1) both forest structures and bird communities underwent evident changes along successional gradients in post-clearcutting environment; (2) bird species richness and community composition in 60- to 70-years-old clearcutting stands still differed from those in 50- to 79-years-old natural stands, in spite of the fact that most forest attributes of clearcutting stands became comparable to those of natural stands after 40 years; and (3) landscape disturbances contributed more than stand characteristics in explaining the lack of convergence of mature forest species, residents, and short-distance migrants in post-clearcutting environment. Our study points out that more regards should be paid to improve the landscape configuration of the managed forests, and implies that old-growth forest retention within logged areas, combined with selection cutting and prolonged logging rotations, can better emulate fire and alleviate forest harvesting effects on bird community assemblages typical of natural boreal ecosystem.     

Preparation and Efficacy of Newcastle Disease Virus DNA Vaccine Encapsulated in PLGA Nanoparticles

Background

Although the Newcastle disease virus (NDV) inactivated vaccines and attenuated live vaccines have been used to prevent and control Newcastle disease (ND) for years, there are some disadvantages. Recently, newly developed DNA vaccines have the potential to overcome these disadvantages. The low delivery efficiency, however, hindered the application of DNA vaccines for ND in practice.

Methodology/Principal Findings

The eukaryotic expression plasmid pVAX1-F (o) DNA that expressed the F gene of NDV encapsulated in PLGA nanoparticles (pFNDV-PLGA-NPs) were prepared by a double emulsion-solvent evaporation method and optimal preparation conditions of the pFNDV-PLGA-NPs were determined. Under the optimal conditions, the pFNDV-PLGA-NPs were produced in good morphology and had high stability with a mean diameter of 433.5±7.5 nm, with encapsulation efficiency of 91.8±0.3% and a Zeta potential of +2.7 mV. Release assay in vitro showed that the fusion gene plasmid DNA could be sustainably released from the pFNDV-PLGA-NPs up to 93.14% of the total amount. Cell transfection test indicated that the vaccine expressed and maintained its bioactivity. Immunization results showed that better immune responses of SPF chickens immunized with the pFNDV-PLGA-NPs were induced compared to the chickens immunized with the DNA vaccine alone. In addition, the safety of mucosal immunity delivery system of the pFNDV-PLGA-NPs was also tested in an in vitro cytotoxicity assay.

Conclusions/Significance

The pFNDV-PLGA-NPs could induce stronger cellular, humoral, and mucosal immune responses and reached the sustained release effect. These results laid a foundation for further development of vaccines and drugs in PLGA nanoparticles.     

Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

Objective

To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model.

Methods

In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.

Results

Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis.

Conclusion

We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.     

Prevalence and Trends of the Abdominal Aortic Aneurysms Epidemic in General Population - A Meta-Analysis

Objective

To conduct a meta-analysis assessing the prevalence and trends of the abdominal aortic aneurysms (AAA) epidemic in general population.

Method

Studies that reported prevalence rates of AAA from the general population were identified through MEDLINE, EMBASE, Web of Science, and reference lists for the period between 1988 and 2013. Studies were included if they reported prevalence rates of AAA in general population from the community. In stratified analyses possible sources of bias, including areas difference, age, gender and diameter of aneurysms were examined. Publication bias was assessed with Egger''s test method.

Results

56 studies were identified. The overall pooled prevalence of AAA was 4.8% (4.3%, 5.3%). Stratified analyses showed the following results, areas difference: America 2.2% (2.2%, 2.2%), Europe 2.5% (2.4%, 2.5%), Australia 6.7% (6.5%, 7.0%), Asia 0.5% (0.3%, 0.7%); gender difference: male 6.0% (5.3%, 6.7%), female 1.6% (1.2%, 1.9%); age difference: 55–64years 1.3% (1.2%, 1.5%), 65–74 years 2.8% (2.7%, 2.9%), 75–84 years1.2%(1.1%, 1.3%), ≥85years0.6% (0.4%, 0.7%); aortic diameters difference: 30–39 mm, 3.3% (2.8%, 3.9%), 40–49 mm,0.7% (0.4%,1.0%), ≥50 mm, 0.4% (0.3%, 0.5%). The prevalence of AAA has decreased in Europe from 1988 to 2013. Hypertension, smoking, coronary artery disease, dyslipidemia, respiratory disease, cerebrovascular disease, claudication and renal insufficiency were risk factors for AAA in Europe.

Conclusion

AAA is common in general population. The prevalence of AAA is higher in Australia than America and Europe. The pooled prevalence in western countries is higher than the Asia. Future research requires a larger database on the epidemiology of AAA in general population.     

Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient’s CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient’s normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.     

Monoclonal antibody disulfide reduction during manufacturing

Manufacturing-induced disulfide reduction has recently been reported for monoclonal human immunoglobulin gamma (IgG) antibodies, a widely used modality in the biopharmaceutical industry. This effect has been tied to components of the intracellular thioredoxin reduction system that are released upon cell breakage. Here, we describe the effect of process parameters and intrinsic molecule properties on the extent of reduction. Material taken from cell cultures at the end of production displayed large variations in the extent of antibody reduction between different products, including no reduction, when subjected to the same reduction-promoting harvest conditions. Additionally, in a reconstituted model in which process variables could be isolated from product properties, we found that antibody reduction was dependent on the cell line (clone) and cell culture process. A bench-scale model using a thioredoxin/thioredoxin reductase regeneration system revealed that reduction susceptibility depended on not only antibody class but also light chain type; the model further demonstrates that the trend in reducibility was identical to DTT reduction sensitivity following the order IgG1λ > IgG1κ > IgG2λ > IgG2κ. Thus, both product attributes and process parameters contribute to the extent of antibody reduction during production.     

Quantitative and Temporal Control of Oxygen Microenvironment at the Single Islet Level

Simultaneous oxygenation and monitoring of glucose stimulus-secretion coupling factors in a single technique is critical for modeling pathophysiological states of islet hypoxia, especially in transplant environments. Standard hypoxic chamber techniques cannot modulate both stimulations at the same time nor provide real-time monitoring of glucose stimulus-secretion coupling factors. To address these difficulties, we applied a multilayered microfluidic technique to integrate both aqueous and gas phase modulations via a diffusion membrane. This creates a stimulation sandwich around the microscaled islets within the transparent polydimethylsiloxane (PDMS) device, enabling monitoring of the aforementioned coupling factors via fluorescence microscopy. Additionally, the gas input is controlled by a pair of microdispensers, providing quantitative, sub-minute modulations of oxygen between 0-21%. This intermittent hypoxia is applied to investigate a new phenomenon of islet preconditioning. Moreover, armed with multimodal microscopy, we were able to look at detailed calcium and K_ATP channel dynamics during these hypoxic events. We envision microfluidic hypoxia, especially this simultaneous dual phase technique, as a valuable tool in studying islets as well as many ex vivo tissues.