Identification of copy number variants in children and adolescents with autism spectrum disorder: a study from Turkey

Molecular Biology Reports - Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as...     

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

Adriamycin (ADR) increases the production of reactive oxygen species (ROS), which diminishes mitochondrial function. Angiotensin-II stimulates mitochondrial ROS generation. The aim of the study was to examine whether angiotensin converting enzyme (ACE) or renin inhibitors protect against ADR-induced mitochondrial function impairment. Rats were divided into five groups as control, ADR, co-treatment ADR with captopril, co-treatment ADR with aliskiren, co-treatment ADR with both captopril and aliskiren. Left ventricular function and blood pressures were assessed at the end of treatment period. Mitochondrial membrane potential (MMP) and ATP levels were determined. ADR treatment decreased the left ventricular pressure and increased the left ventricular end-diastolic pressure. ADR decreased MMP and ATP levels in myocyte mitochondria due to increasing oxidative stress. ADR decreased MMP and ATP levels due to increased oxidative stress in the heart. Inhibitors of ACE and renin caused the elevation of the decreased of MMP and ATP levels. The pathologic changes in electrocardiogram, blood pressure and left ventricular function were decreased by inhibition of Ang-II production. We concluded that inhibitors of angiotensin II are effective against ADR cardiotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.     

Endoscopically visible steam pop during high-energy laser pulmonary vein ablation

A 58-year-old woman with atrial fibrillation underwent laser balloon ablation at our centre. During 12 W ablation in the left superior pulmonary vein, a sudden steam pop was witnessed with displacement of the balloon catheter. Visualisation of the pulmonary vein antrum showed a red discolouration at the last ablation site.The endoscopically assisted laser balloon ablation system (EAS) is a relatively novel technique that is being used to perform pulmonary vein isolation (PVI) in the treatment of atrial fibrillation [1]. The EAS consists of a flexible, compliant balloon for sustained wall contact and a power adjustable laser beam for ablation independent of tissue contact.A 58-year-old woman underwent PVI with the EAS due to drug-refractory, symptomatic and paroxysmal atrial fibrillation. During 12 W ablation at the antrum of the left superior pulmonary vein (LSPV), a sudden steam pop was witnessed, with displacement of the EAS catheter (Fig. 1). Visualisation of the LSPV antrum showed a red discolouration, most likely a haematoma in the antral wall of the LSPV, at the last ablation site. A successful PVI was performed; the red discolouration was still present after 1 h. The patient did not develop symptoms related to the steam pop and echocardiography did not reveal any abnormalities.Open in a separate windowFig. 1Witnessed steam pop during endoscopically assisted ablation. Panel a displays the fifth ablation site in the left superior pulmonary vein (LSPV) where the steam pop occurred. The white ring of exposed tissue is a sign of optimal catheter-wall contact. Panel b displays the LSPV antrum directly after the steam pop. Note the red discolouration which was not present in panel a Steam pops are caused by overheating of myocardial tissue, exceeding 100 ℃, and are preceded by a shift in impedance levels, which cannot be measured with the EAS. Higher energy settings and higher contact force are known to increase the risk of steam pops. Steam pops can lead to tissue disruption and cardiac perforation [2]. However, steam pops appear to be a rare complication with reduced EAS energy settings, which we mostly used in 50 EAS patients, in whom no steam pops were observed [3].     

NT-proBNP during and after primary PCI for improved scheduling of early hospital discharge

Background

The Zwolle Risk Score (ZRS) identifies primary percutaneous coronary intervention (PPCI) patients at low mortality risk, eligible for early discharge. Recently, this score was improved by adding baseline NT-proBNP. However, the optimal timepoint for NT-proBNP measurement is unknown.

Methods

PPCI patients in the On-Time 2 study were candidates. The ZRS and NT-proBNP levels on admission, at 18–24?h, at 72–96?h, and the change in NT-proBNP from baseline to 18–24?h (delta NT-proBNP) were determined. We investigated whether addition of the different NT-proBNP measurements to the ZRS improves the prediction of 30-day mortality. Based on cut-off values reflecting zero mortality at 30?d, patients who potentially could be discharged early were identified and occurrence of major adverse cardiac events (MACE) and major bleeding until 10?d was registered.

Results

845 patients were included. On multivariate analyses, NT-proBNP at baseline (HR 2.09, 95% CI 1.59–2.74, p < 0.001), at 18–24?h (HR 6.83, 95% CI 2.94–15.84), and at 72–96?h (HR 3.32, 95% CI 1.22–9.06) independently predicted death at 30?d. Addition of NT-proBNP to the ZRS improved prediction of mortality, particularly at 18–24?h (net reclassification index 29%, p < 0.0001, integrated discrimination improvement 17%, p < 0.0001). Based on ZRS (<2) or NT-proBNP at 18–24?h (<2500?pg/ml) 75% of patients could be targeted for early discharge at 48?h, with expected re-admission rates of 1.2% due to MACE and/or major bleeding.

Conclusions

NT-proBNP at different timepoints improves prognostication of the ZRS. Particularly at 18–24?h post PPCI, the largest group of patients that potentially could be discharged early was identified.

     

Extending the Schizosaccharomyces pombe Molecular Genetic Toolbox

Targeted alteration of the genome lies at the heart of the exploitation of S. pombe as a model system. The rate of analysis is often determined by the efficiency with which a target locus can be manipulated. For most loci this is not a problem, however for some loci, such as fin1 ⁺, rates of gene targeting below 5% can limit the scope and scale of manipulations that are feasible within a reasonable time frame. We now describe a simple modification of transformation procedure for directing integration of genomic sequences that leads to a 5-fold increase in the transformation efficiency when antibiotic based dominant selection markers are used. We also show that removal of the pku70 ⁺ and pku80 ⁺ genes, which encode DNA end binding proteins required for the non-homologous end joining DNA repair pathway, increases the efficiency of gene targeting at fin1 ⁺ to around 75–80% (a 16-fold increase). We describe how a natMX6/rpl42 ⁺ cassette can be used for positive and negative selection for integration at a targeted locus. To facilitate the evaluation of the impact of a series of mutations on the function of a gene of interest we have generated three vector series that rely upon different selectable markers to direct the expression of tagged/untagged molecules from distinct genomic integration sites. pINTL and pINTK vectors use ura4 ⁺ selection to direct disruptive integration of leu1 ⁺ and lys1 ⁺ respectively, while pINTH vectors exploit nourseothricin resistance to detect the targeted disruption of a hygromycin B resistance conferring hphMX6 cassette that has been integrated on chromosome III. Finally, we have generated a series of multi-copy expression vectors that use resistance to nourseothricin or kanamycin/G418 to select for propagation in prototrophic hosts. Collectively these protocol modifications and vectors extend the versatility of this key model system.     

Novel polymeric microspheres: Synthesis,enzyme immobilization,antimutagenic activity,and antimicrobial evaluation against pathogenic microorganisms

New polymeric microspheres containing azomethine ( 1a ‐ 1c and 2a ‐ 2c ) were synthesized by condensation to compare the enzymatic properties of the enzyme glucose oxidase (GOx) and to investigate antimutagenic and antimicrobial activities. The polymeric microspheres were characterized by elemental analysis, infrared spectra (FT‐IR), proton nuclear magnetic resonance spectra, thermal gravimetric analysis, and scanning electron microscopy analysis. The catalytic activity of the glucose oxidase enzyme follows Michaelis‐Menten kinetics. Influence of temperature, reusability, and storage capacity of the free and immobilized glucose oxidase enzyme were investigated. It is determined that immobilized enzymes exhibit good storage stability and reusability. After immobilization of GOx in polymeric supports, the thermal stability of the enzyme increased and the maximum reaction rate (V_max) decreased. The activity of the immobilized enzymes was preserved even after 5 months. The antibacterial and antifungal activity of the polymeric microspheres were evaluated by well‐diffusion method against some selected pathogenic microorganisms. The antimutagenic properties of all compounds were also examined against sodium azide in human lymphocyte cells by micronuclei and sister chromatid exchange tests.     

Life-threatening perforation of a defibrillation lead

We describe cardiac perforation of a Riata implantable cardioverter defibrillator (ICD) shock lead in a 76-year-old male nine days after implantation of a prophylactic ICD. Since there are more reports of increased risk of cardiac perforations with the Riata lead, we advise cautious use of this lead. (Neth Heart J 2009;17:113–4.)