Under-Utilization of Implantable Cardioverter Defibrillators in Patients with Heart Failure - The Current State of Sudden Cardiac Death Prophylaxis

BackgroundDespite ACC/AHA guidelines indicating implantable cardioverter defibrillator (ICD) as class I therapy for primary prevention of sudden cardiac death in patients with EF≤35%, ICD utilization rates in real world practice have been low.ObjectiveTo determine the rate of ICD implantation at a tertiary care academic center and to assess the reasons for under-utilization of the same.MethodsReview of a prospectively collected database which included all patients diagnosed with an EF≤35% was performed to assess the rate of ICD implantation and mortality. Reasons for non-implantation of ICD were then assessed from detailed chart review.ResultsA total of 707 patients (age 69.4 ± 14.1 years) with mean EF of 26±7% were analyzed. Only 28% (200/707) of patients had ICDs implanted. Mortality was lower in the group with ICD (25% vs 37%, p=0.004). When patients who either died or were lost to follow-up prior to 2005 were excluded, ICD utilization rate was still low at 37.6%. The most common reason for non-implantation of ICD was physicians not discussing this option with their patients. Patient refusal was the second most common reason.ConclusionsICD Implantation rates for primary prevention of SCD in patients with EF≤35% is low. Physician and patient education should be addressed to improve the utilization rates.Key words: Implantable cardioverter-defibrillator, Outcomes, sudden cardiac death     

Hydrogen sulfide removal performance of a bio-trickling filter employing Thiobacillus thiparus immobilized on polyurethane foam under various starvation regimes

In the present study a biotrickling filter (BTF) with countercurrent gas/liquid flow packed with open-pore polyurethane foam — as a carrier of Thiobacillus thioparus (DSMZ5368) — was subjected to various starvation regimes such as non-contaminant loading, idleness, and complete shutdown. During the starvation periods specific oxygen uptake rates of microorganisms (SOUR) on packing were monitored. The BTF was subjected to non-contaminant loading (up to 16 h), cyclic non-contaminant loading (for 4 days) and gas shut-off (up to 24 h), and it recovered to its pre-starvation removal efficiency within a 2 ～ 3 h period after resuming normal operating conditions. The recovery time values obtained during the runs in which these starvation regimes were imposed could be indirectly correlated with the corresponding SOUR values suggesting that the recovery time after such starvation regimes are dependent on the degree to which the aerobic biological activity has been reduced as a result of the imposed starvation regime. In the case of the complete shutdown of the BTF, the recovery time increased substantially after 1 and 2 days of complete shutdown, and after 5 days of complete shutdown the pre-starvation removal efficiency was not achieved even after 12 days of normal operation.     

Twelve-Year Cardiovascular and Mortality Risk in Relation to Smoking Habits in Type 2 Diabetic and Non-Diabetic Men: Tehran Lipid and Glucose Study

Introduction

To examine the associations between smoking and cardiovascular disease (CVD) / coronary heart disease (CHD) and all-cause mortality events in men with and without type 2 diabetes (T2D) in a Middle Eastern cohort during a median follow-up of 12 years.

Methods

The study population included 2230 subjects aged ≥ 40 years, free from CVD, comprised of 367 participants with diabetes (21.2% current smokers) and 1863 without (27.3% current smokers). Multivariate Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for smoking (considering different definitions) for those with and without diabetes. Potential confounding factors including age, body mass index, estimated Glomerular Filtration Rate, hypertension, hypercholesterolemia and educational level were entered in the multivariate analysis.

Results

In men with diabetes, the HR (95% CI) of comparing current and non-smokers was 1.25 (0.74–2.12) for incident CHD, 1.52 (0.96–2.40) for CVD and 2.10 (1.27–3.47) for mortality events; the corresponding values for men without diabetes were 1.65 (1.24–2.20), 1.70 (1.30–2.22) and 1.72 (1.14–2.58), respectively (all P values for interactions > 0.46). After pooling past smokers with current smokers, among diabetic individuals there was no significant risk for CVD [1.29 (0.89–1.86)] or mortality events [1.25 (0.81–1.92)]; however, among non-diabetic individuals the HRs of current/past smokers reached significant levels for CVD [1.53 (1.23–1.91)] but not for mortality outcomes (all P values for interactions > 0.51).

Conclusions

The strength of the associations between smoking habits and incident CVD/CHD and mortality events from all causes did not differ significantly among diabetic and non-diabetic participants. Therefore, a comprehensive community-based smoking prevention program is important, given the increasing trend of smoking among the Iranian population regardless of diabetes status.     

Spectroscopy and computational studies on the interaction of octyl,dodecyl, and hexadecyl derivatives of anionic and cationic surfactants with adenosine deaminase

Effects of sodium (octyl, dodecyl, hexadecyl) sulfate and their cationic analogous on the structure of adenosine deaminase (ADA) were investigated by fluorescence and circular dichroism spectroscopy as well as molecular dynamics simulation and docking calculation. Root-mean-square derivations, radius of gyration, solvent accessible surface area, and radial distribution function were obtained. The results showed that anionic and cationic surfactants reduce protein stability. Cationic surfactants have more effect on the ADA structure in comparison with anionic surfactants. More concentration and longer surfactants are parallel to higher denaturation. Furthermore, aggregation in the presence of anionic surfactants is more than cationic surfactants. Docking data showed that longer surfactants have more interaction energy and smaller ones bound to the active site.     

Effects of surfactant, salt and solvent on the structure and activity of adenosine deaminase: molecular dynamic and spectrophotometric studies

Effects of sodium dodecyl sulfate, dodecyltrimethylammonium bromide, sodium chloride, sodium sulfate, methanol and ethanol, on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis, circular dichroism spectrophotometry and molecular dynamics (MDs) studies. Relative activity, experimental and computational helix content, total accessible surface area (ASA) and exposed charged surface area (ECSA) were obtained. The relative activity of ADA in the absence and the presence of denaturants were compared with structural results. It was shown that an increase in the surface area and a decrease in the amount of helicity are associated with a decrease in the activity of ADA.     

Design and biological evaluation of phenyl-substituted analogs of beta-phenylethylidenehydrazine

Beta-Phenylethylidenehydrazine (PEH) has been demonstrated previously to be an inhibitor of gamma-aminobutyric acid transaminase (GABA-T) and to cause a marked increase in rat brain levels of GABA, a major neurotransmitter. A group of PEH analogs, possessing a variety of substituents (Me, OMe, Cl, F, and CF3) at the 2-, 3-, and 4-positions of the phenyl ring, were synthesized for evaluation as inhibitors of GABA-T. The details of the synthesis and chemical characterization of the analogs are described. Preliminary in vitro screening for GABA-T inhibition showed that all the analogs possessed activity against this enzyme, although substitution of CF3 at the 2- and 4-positions caused reduced activity. One of the drugs, 4-fluoro-beta-phenylethylidenehydrazine, was investigated further ex vivo, where it was shown to inhibit GABA-T, elevate brain levels of GABA, and decrease levels of glutamine, similar to the profile observed previously for PEH.     

The clinical significance of miR-335, miR-124, miR-218 and miR-484 downregulation in gastric cancer

Gastric cancer (GC) is one of the leading types of malignancy worldwide, particularly in Asian populations. Although the exact molecular mechanism of GC development remains unknown, microRNA (miRNA) has recently been shown to be involved. The current study aims to investigate the expression levels of bioinformatically ranked miRNAs in gastric tissues. Using bioinformatics tools, we prioritized miRNAs thought to be implicated in GC. Furthermore, polyA-qPCR was used to validate bioinformatics findings in 40 GC, 31 normal gastric tissue (NG) and 45 gastric dysplasia (GD) samples. As identified by bioinformatics analysis, miR-335 was shown to be the top-ranked miRNA implicated in GC. Moreover, a significant downregulation of miR-335, miR-124, miR-218 and miR-484 was found in GC and GD compared to NG samples. We found bioinformatics to be an efficient approach to finding candidate miRNAs relevant to GC development. Finally, the findings show that downregulation of miRNAs such as miR-124 and miR-218 in gastric tissue can be a significant indicator for neoplastic transformation.     

AiiA lactonase disrupts N-acylhomoserine lactone and attenuates quorum-sensing-related virulence in Pectobacterium carotovorum EMPCC

Enzymatic degradation of N-acyl homoserine lactone (NAHL) was found to interfere with the quorum sensing (QS) system and related functions in several soil bacteria. In this research, the NAHL lactonase gene aiiA was amplified using aiiA-7F/aiiA7R PCR primers from the quorum sensing inhibitor rhizobacterium Bacillus sp. strain DMS133, and cloned. The plasmid pME7075, carrying the DMS133 aiiA gene under the constitutive lac promoter, was introduced into the plant pathogen Pectobacterium carotovorum EMPCC, creating strain EMPCC/aiiA. Heterologous expression of the DMS133 aiiA gene in EMPCC severely reduced the accumulation of the NAHL throughout growth, and completely prevented pigmentation of the CV026 bioreporter strain. Virulence analysis revealed that the P. carotovorum strain EMPCC/aiiA expressing AiiA lactonase had drastically reduced tissue maceration activity compared with the wild type EMPCC strain. These results provide evidence that AiiA plays an important role in the quorum quenching ability of Bacillus sp. DMS133 whose AHL degradation capacity was investigated previously. In addition, the communication signal-inactivation approach represents a promising strategy for the prevention of diseases in which virulence is regulated by QS signal molecules.