Minimally invasive colon resection is associated with a persistent increase in plasma PlGF levels following cancer resection

Background  

Minimally invasive colorectal resection (MICR) is associated with persistently elevated plasma VEGF levels that may stimulate angiogenesis in residual tumor foci. Placenta growth factor (PlGF) stimulates neovascularization in tumors by modulating VEGF’s effects. This study’s purpose was to determine the impact of MICR on blood PlGF levels in cancer patients (Study A) and to compare PreOp levels in patients with cancer and benign (BEN) disease (Study B).     

Whisker maps in marsupials: nerve lesions and critical periods

In the wallaby, whisker-related patterns develop over a protracted period of postnatal maturation in the pouch. Afferents arrive simultaneously in the thalamus and cortex from postnatal day (P) 15. Whisker-related patterns are first seen in the thalamus at P50 and are well formed by P73, before cortical patterns first appear (P75) or are well developed (P85). This study used the slow developmental sequence and accessibility of the pouch young to investigate the effect of nerve lesions before afferent arrival, or at times when thalamic patterns are obvious but cortical patterns not yet formed. The left infraorbital nerve supplying the whiskers was cut at P0-93 and animals were perfused at P112-123. Sections through the thalamus (horizontal plane) and cortex (tangential) were reacted for cytochrome oxidase to visualize whisker-related patterns. Lesions of the nerve at P2-5, before innervation of the thalamus or cortex, resulted in an absence of patterns at both levels. Lesions from P66-77 also disrupted thalamic and cortical patterns, despite the fact that thalamic patterns are normally well established by P73. Lesions from P82-93 resulted in normal thalamic and cortical patterns. Thus, despite the wallaby having clearly separated times for the development of patterns at different levels of the pathway, these results suggest a single critical period for the thalamus and cortex, coincident with the maturation of the cortical pattern. Possible mechanisms underpinning this critical period could include dependence of the thalamic pattern on corticothalamic activity or peripheral signals to allow consolidation of thalamic barreloids.     

Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties

Emergence of bacterial resistance is a major issue for all classes of antibiotics; therefore, the identification of new classes is critically needed. Recently we reported the discovery of platensimycin by screening natural product extracts using a target-based whole-cell strategy with antisense silencing technology in concert with cell free biochemical validations. Continued screening efforts led to the discovery of platencin, a novel natural product that is chemically and biologically related but different from platensimycin. Platencin exhibits a broad-spectrum Gram-positive antibacterial activity through inhibition of fatty acid biosynthesis. It does not exhibit cross-resistance to key antibiotic resistant strains tested, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococci. Platencin shows potent in vivo efficacy without any observed toxicity. It targets two essential proteins, beta-ketoacyl-[acyl carrier protein (ACP)] synthase II (FabF) and III (FabH) with IC50 values of 1.95 and 3.91 microg/ml, respectively, whereas platensimycin targets only FabF (IC50 = 0.13 microg/ml) in S. aureus, emphasizing the fact that more antibiotics with novel structures and new modes of action can be discovered by using this antisense differential sensitivity whole-cell screening paradigm.     

Characterization of the shark myelin Po protein

Myelin, the insulating sheath made by extensive plasma membrane wrapping, is dependent on the presence of highly adhesive molecules that keep the two sides of the membrane in tight contact. The Po glycoprotein (Po) is the major component of the peripheral nervous system (PNS) myelin of mammals. The exact role that Po protein has played in the evolution of myelin is still unclear, but several phylogenetic observations suggest that it is a crucial component in the development of myelin as a multi-lamellar membrane structure. Sharks, which appeared in the fossil record about 400 million years ago, are the first fully myelinated organisms. In this study we investigated the expression pattern of shark myelin Po to suggest a way it might have played a role in the evolution of myelin in the central nervous system. We found that sharks have more than two isoforms (32, 28 and 25 kD), and that some of these might not be fully functional because they lack the domains known for Po homophilic adhesion.     

Comparison of abciximab with "high-dose" tirofiban in patients undergoing percutaneous coronary intervention

BACKGROUND: The TARGET study has been criticised for sub-optimal platelet inhibition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiban (hd-tirofiban) to standard dose of abciximab for patients undergoing percutaneous coronary intervention (PCI). METHODS: We assessed consecutive patients who received either hd-tirofiban (25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were obtained in all cases. RESULTS: Over an 18-month period, 109 patients who received hd-tirofiban were compared with 110 patients who received abciximab. Both hd-tirofiban and abciximab groups had acute coronary syndromes in 86% and 80% and diabetes in 10% and 13% respectively. Most patients had coronary stent implantation (96% vs. 98%). Thrombocytopenia (platelet count< 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2% of patients receiving abciximab (p = 0.566). Bleeding requiring transfusion occurred in 7.3% and 3% of patients respectively (p = 0.118). Peri-procedural troponin rise was 0.9% in patients receiving hd-tirofiban and 5.5% in patients receiving abciximab (p = 0.07). MACE (Myocardial infarction, Stroke, Revascularisation and Death) at 6 months was 23% in the hd-tirofiban group and 20% in the abciximab group (p = 0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban (one ampoule) and AUD 1,350 for abciximab (3 ampoules). CONCLUSION: There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group however, the overall 6-month MACE rates were similar in both groups. There was a considerable cost-saving with the use of hd-tirofiban. A prospective randomised trial of hd-tirofiban vs. abciximab is warranted.     

Genetic and environmental etiology of nicotine use in sri lankan male twins

Little is known about the prevalence and etiology of tobacco use in Asian populations. This study aims to test whether the finding of substantial heritability for tobacco-related phenotypes in Western populations is generalizable to developing countries. The twin method was used to estimate the relative contribution of genetic and environmental influences on nicotine-related phenotypes. Participants were selected from the population based Sri Lankan Twin Registry. The Composite International Diagnostic Interview was administered to 1,804 male individuals to assess five phenotypes: nicotine use; desire and unsuccessful attempts to quit smoking; subjective feeling of being tobacco dependent; and two DSM-IV diagnoses; nicotine dependence and nicotine withdrawal. Almost one-third of the male twins were life-time smokers. The genetic results were consistent with the previously reported findings from Western and Chinese populations, in that the nicotine use traits were significantly heritable, with environmental influences being of the non-shared nature. The results derived from the Causal Contingent Common pathway model (CCC) supported previous findings that show that liabilities to regular smoking and subsequent problem smoking have both shared and specific genetic influences.     

A difference-matrix metaheuristic for intensity map segmentation in step-and-shoot IMRT delivery

At an intermediate stage of radiation treatment planning for IMRT, most commercial treatment planning systems for IMRT generate intensity maps that describe the grid of beamlet intensities for each beam angle. Intensity map segmentation of the matrix of individual beamlet intensities into a set of MLC apertures and corresponding intensities is then required in order to produce an actual radiation delivery plan for clinical use. Mathematically, this is a very difficult combinatorial optimization problem, especially when mechanical limitations of the MLC lead to many constraints on aperture shape, and setup times for apertures make the number of apertures an important factor in overall treatment time. We have developed, implemented and tested on clinical cases a metaheuristic (that is, a method that provides a framework to guide the repeated application of another heuristic) that efficiently generates very high-quality (low aperture number) segmentations. Our computational results demonstrate that the number of beam apertures and monitor units in the treatment plans resulting from our approach is significantly smaller than the corresponding values for treatment plans generated by the heuristics embedded in a widely use commercial system. We also contrast the excellent results of our fast and robust metaheuristic with results from an 'exact' method, branch-and-cut, which attempts to construct optimal solutions, but, within clinically acceptable time limits, generally fails to produce good solutions, especially for intensity maps with more than five intensity levels. Finally, we show that in no instance is there a clinically significant change of quality associated with our more efficient plans.