Cardiovascular Risk Reduction is Important for Improving Patient and Graft Survival After Ligation and Bypass Surgery for Popliteal Artery Aneurysm

OBJECTIVES: To report outcomes following ligation and bypass (LGB) surgery for popliteal artery aneurysm (PAA) and study factors influencing patient and graft survival. MATERIALS AND METHODS: A retrospective review of patients undergoing LGB surgery for PAA between September 1999 and August 2012 at a tertiary referral vascular unit was performed. Primary graft patency (PGP), primary-assisted graft patency (PAGP), and secondary graft patency (SGP) rates were calculated using survival analyses. Patient, graft aneurysm-free survival (GAFS), aneurysm reperfusion-free survival (ARFS), and amputation-free survival (AFS) rates were also calculated. Log-rank testing and Cox proportional hazards modeling were used to perform univariate and multivariate analysis of influencing factors, respectively. RESULTS: Eighty-four LGB repairs in 69 patients (mean age 71.3 years, 68 males) were available for study. The 5-year PGP, PAGP, SGP, and patient survival rates were 58.1%, 84.4%, 85.2%, and 81.1%, respectively. On multivariate analysis, the principal determinants of PGP were urgency of operation ( P = .009) and smoking status ( P = .019). The principal determinants of PAGP were hyperlipidemia status ( P = .048) and of SGP were hyperlipidemia ( P = .042) and cerebrovascular disease (CVD) status ( P = .045). The principal determinants of patient survival were previous myocardial infarction ( P = .004) and CVD ( P = .001). The 5-year GAFS, ARFS, and AFS rates were 87.9%, 91.6%, and 96.1%, respectively. CONCLUSION: This study has shown that traditional cardiovascular risk factors, such as a smoking and ischemic heart disease, are the most important predictors of early graft failure and patient death following LGB surgery for PAA

Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer

The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5′-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion ‘rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival

Multiscale Coarse-Graining of the Protein Energy Landscape

A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states

Omics-based molecular techniques in oral pathology centred cancer: Prospect and challenges in Africa

: The completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have contributed immensely to individualized/personalized medicine in the developed world.At the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratifcation of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the profciency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among diferent human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences

Oblivious symmetric alternation

1 Introduction The symmetric alternation class (Sp2) was introduced independently by Russelland Sundaram [16] and by Canetti [5]. The class S p 2 contains languages havingan interactive proof system of the following type. The proof system consists o

Survey of ankle-brachial pressure index use and its perceived barriers by general practitioners in the UK.

BACKGROUND: Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle-brachial pressure index (ABPI) is the recommended diagnostic tool for PAD. PURPOSE: We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice. METHODS: GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle-brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study. RESULTS: All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use. CONCLUSIONS: Targeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option