Triple-site biventricular pacing in patients undergoing cardiac resynchronization therapy: a feasibility study.

AIMS: To evaluate implantation safety and efficiency of triple-site (double left-single right) cardiac resynchronization therapy (CRT) and to assess the outcome of this procedure. METHODS AND RESULTS: Twenty-six patients with New York Heart Association (NYHA) class III-IV, left ventricular ejection fraction (EF) < or = 35%, and QRS > or = 120 ms underwent triple-site CRT. Procedural course and complications were analysed. NYHA class, QRS duration, echocardiographic parameters, peak oxygen consumption (VO(2)max), and 6 min walking distance (6MWD) were assessed at baseline and after 3 months. Responders were defined by survival, by no re-hospitalization for heart failure, and by >10% EF, VO(2)max, and 6MWD increase. Implantation was successful in 22 patients (84.6%). Procedure duration (199.1 min) and fluoroscopy time (38.7 min) were higher than in standard procedures. Two clinically silent coronary sinus dissections occurred intra-operatively; one phrenic nerve stimulation and one pocket infection were observed during follow-up. After 3 months of CRT, a significant reduction (P < 0.05) of NYHA class, increment of VO(2)max, 6MWD, EF, and improvement of indices of dyssynchrony were observed. Response rate in the studied group was 95.4%. CONCLUSION: Triple-site resynchronization appears to be a safe and efficient treatment method, with high response rate. Further studies are needed to evaluate the role of this pacing mode in CRT.     

P1PK,GLOB, and FORS Blood Group Systems and GLOB Collection: Biochemical and Clinical Aspects. Do We Understand It All Yet?

Antigens belonging to the P1PK, GLOB, and FORS blood group systems and the GLOB blood group collection represent a closely related set of 13 glycosphingolipids (GSLs). They are synthesized by the coordinated action of glycosyltransferases, encoded by at least 7 different loci. Three of these enzymes show either different activity or a different mRNA expression profile due to genetic polymorphisms, resulting in blood group diversity. In recent years, significant progress has been made in understanding the molecular background and biological functions of these GSLs. Their medical significance is often related to the existence of natural antibodies, as they may cause complications after transfusions and during pregnancies. In addition, GSLs belonging to these blood group systems are receptors for several pathogens. This review summarizes the present knowledge about the complicated network of enzymatic interactions leading to synthesis of these GSLs, as well as their clinical implications.     

Cell-density-dependent regulation of neural precursor cell function

Stress-induced reductions of neural precursor cells from the subgranular zone of the hippocampal dentate gyrus have been linked to impaired neurogenesis and cognitive dysfunction. Given the importance of redox state in regulating multiple damage-responsive pathways in the CNS, we hypothesize that oxidative stress plays a major role in affecting neurogenesis and subsequent cognitive function after cell injury/depletion. Using an in vitro system, we showed that the level of reactive oxygen species (ROS), which depend critically on changes in cell density, were significantly higher in neural precursor cells when compared with other primary and transformed cell lines. ROS were significantly elevated ( approximately 4-fold) under low- (<1 x 10(4) cells per cm(2)) versus high-density (>1 x 10(5) cells per cm(2)) conditions. Higher ROS levels found at lower cell densities were associated with elevated proliferation and increased metabolic activity. These ROS were likely a result of altered mitochondrial function that ultimately compromised the growth rate of cells. At high cell densities, intracellular ROS and oxidative damage were reduced in concert with an increased expression of mitochondrial superoxide dismutase 2. Our finding that DNA-damage-induced depletion of neural precursor cells in the subgranular zone of mice also led to increased ROS and altered proliferation validated our in vitro system. Increased ROS and proliferation associated with the reduction of precursor cell numbers both in vitro and in vivo could be reversed with the antioxidant alpha-lipoic acid. These data showed that neural precursor cells were predisposed to microenvironmental cues that regulate redox-sensitive pathways to control cellular proliferation after CNS damage.     

The National Alpha-1 Antitrypsin Deficiency Registry in Poland

Abstract

The alpha-1 antitrypsin deficiency (AATD) targeted screening program, together with the National Registry, were established in Poland in 2010 soon after the AATD diagnostics became available. Between 2010 and 2014 a total of 2525 samples were collected from respiratory patients countrywide; 55 patients with severe AAT deficiency or rare mutations were identified and registered, including 36 PiZZ subjects (65%). The majority of AATD patients were diagnosed with COPD (40%) or emphysema (7%), but also with bronchial asthma (16%) and bronchiectasis (13%). Therefore, the registry has proved instrumental in setting-up the AATD-dedicated network of respiratory medical centres in Poland. Since augmentation therapy is not reimbursed in our country, the smoking cessation guidance, optimal pharmacotherapy of respiratory symptoms as well the early detection, and effective treatment of exacerbations is absolutely essential.     

Advanced Structural and Technological Method of Reducing Distortion in Thin-Walled Welded Structures

The article presents an innovative method of reducing welding distortions of thin-walled structures by introducing structural and technological changes. The accuracy of the method was demonstrated on the example of welding the stub pipes to the outer surface of a thin-walled tank with large dimensions, made of steel 1.4301 with a wall thickness of 1.5 × 10⁻³ (m). During traditional Gas Tungsten Arc Welding (GTAW), distortions of the base are formed, the flatness deviation of which was 11.9 × 10⁻³ (m) and exceeded the permissible standards. As a result of structural and technological changes, not only does the joint stiffness increase, but also a favorable stress state is introduced in the flange, which reduces the local welding stresses. Numerical models were developed using the finite element method (FEM), which were used to analyze the residual stresses and strains pre-welding, in extruded flanges, in transient, and post-welding. The results of the calculations for various flanges heights show that there is a limit height h = 9.2 × 10⁻³ (m), above which flange cracks during extrusion. A function for calculating the flange height was developed due to the required stress state. The results of numerical calculations were verified experimentally on a designed and built test stand for extrusion the flange. The results of experimental research confirmed the results of numerical simulations. For further tests, bases with a flange h = 6 × 10⁻³ (m) were used, to which a stub pipe was welded using the GTAW method. After the welding process, the distortion of the base was measured with the ATOS III scanner (GOM a Zeiss company, Oberkochen, Germany). It has been shown that the developed methodology is correct, and the introduced structural and technological changes result in a favorable reduction of welding stresses and a reduction in the flatness deviation of the base in the welded joint to 0.39 × 10⁻³ (m), which meets the requirements of the standards.     

Rationale and feasibility of mucin expression profiling by qRT-PCR as diagnostic biomarkers in cytology specimens of pancreatic cancer

Background

Aberrantly expressed mucin glycoproteins (MUC) play important roles in pancreatic ductal adenocarcinoma (PDAC), yet their use as a diagnostic aid in fine-needle aspiration biopsy (FNAB) is poorly documented. The aim of this study was to investigate the rationale and feasibility of mucin (MUC1, MUC2, MUC3, MUC4, MUC5AC, and MUC6) expression profiling by RT-PCR for diagnostic applications in cytology.