The first 124 nucleotides of the E7 coding sequences of HPV16 can render the HPV11 genome transformation competent.

The human papillomavirus (HPV) type 16 is associated with the majority of cervical tumors and is capable of oncogenically transforming cells in culture. HPV type 11 is rarely associated with malignant lesions and does not transform cells in vitro. While the E7 of HPV16 is necessary and sufficient for transformation of rodent cells, the E7 gene of HPV11 is not transforming. In the present report we demonstrate that the HPV11 genome, with the first 124 nucleotides of the HPV16 E7 open reading frame fused to the last 198 nucleotides of the HPV11 E7 open reading frame, becomes transformation competent.     

Studies on carboxymethylcellulose: Conductivity measurements of solutions, 2

The conductivity behaviour of carboxymethylcellulose (CMC) solutions was studied using different types of neutralizing reagents (LiOH, NaOH, KOH); the following order of conductance of CMC solutions was observed: Li⁺ < Na⁺ < K⁺. This conductance behaviour of CMC solutions with respect to the size of counterions is explained qualitatively as well as quantitatively. Binding of Li⁺, Na⁺ and K⁺ ions onto the polymer molecule and the influence of the degree of substitution, ,DS , on the conductivity of CMC were also investigated. The conductivity of CMC solutions as well as the fraction of bound counterions increase with increasing DS , at a given degree of neutralization (α) for each type of counterion. The effect of DS on the polymer charge fraction, i/s, is in line with the counterion condensation phenomena of Oosawa. The results regarding the dependence of the equivalent conductance of the polyion, Δ_p, on DS are compared with literature data.     

Loss of base excision repair in aging rat neurons and its restoration by DNA polymerase beta

Synthetic staggered oligodeoxynucleotide duplexes are formed by annealing a 5'-32P-labeled 14-mer with four different 21-mers. These duplexes have either a correct or mismatched base pair at 3'-end of the primer. With these model template primers the ability of neuronal extracts, obtained from rats of different ages, to extend the primer to the predicted length was tested. While the neuronal extracts of all ages were able to degrade the 14-mer to shorter lengths, extension of the primers in general and in particular, the mismatched, is achieved only feebly by the young and adult neuronal extracts and undetectable with old neuronal extracts. The possibility of restoring the lost activity by supplementing the neuronal extracts with pure DNA polymerases was examined. Of the three polymerases tested (calf thymus alpha polymerase, E. coli DNA polymerase I and rat liver DNA polymerase beta) only polymerase beta gave consistent and encouraging results although the extension was slow and distributive in nature and mismatched primers were extended much less efficiently than the correctly paired primer. However, significantly improved extension, including those of mismatched primers, was achieved by prior removal of mismatched bases in a preincubation with just the neuronal extracts (3'-5'exonuclease activity) followed by extension by the added polymerase beta and dNTPs in the presence of Mn(2+) instead of the usual Mg(2+). These results are taken to indicate that the activity of polymerase beta in brain cells is compromised with age and that this deficit can be corrected in vitro by the addition of pure recombinant rat liver polymerase beta under appropriate conditions.     

The use of Statins in the perioperative period

3 Hydroxy 3 Methyl Glutaryl Coenzyme A Reductase Inhibitors’ (statins) are increasingly being used in patients with cardiovascular disease. The Scottish Intercollegiate Guidelines Network (SIGN) and National Institute of Health and Clinical Excellence (NICE) recommend their use in primary and secondary prevention of cardiovascular events. Patients on preoperative statins will frequently present for surgical procedures. The increase in adverse cardiovascular outcomes in high risk patients if statins are withheld in the immediate postoperative period should be weighed against the small but serious risk of rhabdomyolysis associated with statins. The potential for drug interactions should be considered when prescribing for patients on statins.     

Bioactive nano‐fibrous scaffold for vascularized craniofacial bone regeneration

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano‐fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)‐poly (ε) caprolactone (PCL)‐Hydroxyapatite based bioceramic (HAB), namely, PVA‐PCL‐HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA‐PCL‐HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA‐PCL‐HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics.     

Absence of a Primary Role for <Emphasis Type="Italic">SCN10A</Emphasis> Mutations in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Prior reports have identified associations between SCN10A and cardiac disorders, such as atrial fibrillation and Brugada syndrome. We evaluated SCN10A in 151 probands with ARVD/C. In this cohort, 10 putatively pathogenic SCN10A variants were identified, including a novel frameshift insertion. Despite a known role for the encoded protein in peripheral nerve function, the proband with the frameshift variant had no discernible neurological abnormalities. Arrhythmic phenotypes were not different between those with a rare variant in SCN10A and those without. The prevalence of rare variants in SCN10A was similar among ARVD/C probands with and without a desmosome mutation and similar among healthy Caucasian controls. These results indicate the absence of a primary role for SCN10A mutations in ARVD/C.     

Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors

Angioedema is a rare, potentially life-threatening adverse event of renin-angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients ≥100 and a duration of ≥8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.