Contegra conduit for reconstruction of the right ventricular outflow tract: a review of published early and mid-time results

<p>Abstract</p> <p>Objective</p> <p>The valved conduit Contegra (bovine jugular vein) has being implanted for more than 7 years in the right ventricular outflow tract and it is noted that the available reports have been mixed. The aim of this study is to review the reported evidence in the literature.</p> <p>Methods</p> <p>Search of the relevant literature for the primary endpoints of operative mortality and morbidity and secondary endpoints of follow-up haemodynamic performance including severe stenosis, regurgitation and need for reintervention are presented.</p> <p>Results</p> <p>We selected and analysed 17 series including 767 patients. Commonest indication was Fallot's tetralogy. Operative mortality was 2.6%. Operative morbidity was 13.9%. In follow-up, the incidence of intraconduit stenosis was 10.9% (incidence of stenosis for the 12 millimetre conduit was 83.3% in one series) and that of at least moderate regurgitation was 6.3%.</p> <p>The aspirin users had a stenosis incidence of 10.5% compared to the non-users had a stenosis incidence of 9.6%.</p> <p>Conclusion</p> <p>A dissent on the performance of the Contegra is discussed, while results are satisfactory in the majority of studies apart for the smallest conduits (12 and 14 millimetre), suggesting an association to compromised run-off. The role of aspirin as antithrombotic modulator remains controversial.</p

Seasonal effects of a hydropeaking dam on a downstream benthic macroinvertebrate community

Peer Reviewe

Highly Active Microbial Phosphoantigen Induces Rapid yet Sustained MEK/Erk- and PI-3K/Akt-Mediated Signal Transduction in Anti-Tumor Human γδ T-Cells

BACKGROUND: The unique responsiveness of Vgamma9Vdelta2 T-cells, the major gammadelta subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current gammadelta T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human gammadelta T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR)-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vgamma9Vdelta2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), produced by Eubacteria and Protozoa, and examined its gammadelta T-cell activation and anti-tumor properties. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a comparative study between HMB-PP and the anti-CD3epsilon monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular gammadelta T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vgamma9(+) T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including gammadelta T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vgamma9(+) TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains gammadelta T-cell activation upon re-stimulation. This ultimately translates in potent human gammadelta T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, CONCLUSIONS/SIGNIFICANCE: The development of efficient cancer immunotherapy strategies critically depends on our capacity to maximize anti-tumor effector T-cell responses. By characterizing the intracellular mechanisms of HMB-PP-mediated activation of the highly cytotoxic Vgamma9(+) T-cell subset, our data strongly support the usage of this microbial antigen in novel cancer clinical trials

Optimizing the two-step floating catchment area method for measuring spatial accessibility to medical clinics in Montreal

<p>Abstract</p> <p>Background</p> <p>Reducing spatial access disparities to healthcare services is a growing priority for healthcare planners especially among developed countries with aging populations. There is thus a pressing need to determine which populations do not enjoy access to healthcare, yet efforts to quantify such disparities in spatial accessibility have been hampered by a lack of satisfactory measurements and methods. This study compares an optimised and the conventional version of the two-step floating catchment area (2SFCA) method to assess spatial accessibility to medical clinics in Montreal.</p> <p>Methods</p> <p>We first computed catchments around existing medical clinics of Montreal Island based on the shortest network distance. Population nested in dissemination areas were used to determine potential users of a given medical clinic. To optimize the method, medical clinics (supply) were weighted by the number of physicians working in each clinic, while the previous year's medical clinic users were computed by ten years age group was used as weighting coefficient for potential users of each medical clinic (demand).</p> <p>Results</p> <p>The spatial accessibility score (SA) increased considerably with the optimisation method. Within a distance of 1 Km, for instance, the maximum clinic accessible for 1,000 persons is 2.4 when the conventional method is used, compared with 27.7 for the optimized method. The t-test indicates a significant difference between the conventional and the optimized 2SFCA methods. Also, results of the differences between the two methods reveal a clustering of residuals when distance increases. In other words, a low threshold would be associated with a lack of precision.</p> <p>Conclusion</p> <p>Results of this study suggest that a greater effort must be made ameliorate spatial accessibility to medical clinics in Montreal. To ensure that health resources are allocated in the interest of the population, health planners and the government should consider a strategy in the sitting of future clinics which would provide spatial access to the greatest number of people.</p

Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference

<p>Abstract</p> <p>Background</p> <p>Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas.</p> <p>Methods</p> <p>In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry.</p> <p>Results</p> <p>We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors.</p> <p>Conclusion</p> <p>Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer.</p

Corpora amylacea negatively correlate with hippocampal tau pathology in Alzheimer’s disease

Introduction Severity and distribution of aggregated tau and neurofibrillary tangles (NFT) are strongly correlated with the clinical presentation of Alzheimer’s disease (AD). Clearance of aggregated tau could decrease the rate of NFT formation and delay AD onset. Recent studies implicate corpora amylacea (CA) as a regulator of onset or accumulation of tau pathology. Normally, CA clear brain waste products by amassing cellular debris, which are then extruded into the cerebrospinal fluid to be phagocytosed. The proper functioning of CA may slow progression of AD-associated NFT pathology, and this relationship may be influenced by amount and distribution of phospho-tau (pTau) produced, age, sex, and genetic risk. Objective The goal of this study was to determine if CA size and number are associated with hippocampal location and local pTau severity while accounting for variations in age, sex, and genetic risk. Methods Postmortem brain hippocampal tissue sections from 40 AD and 38 unaffected donors were immunohistochemically stained with AT8 (pTau) and counter stained with periodic acid Schiff (PAS). Stained sections of the CA1 and CA3 regions of the hippocampus were analyzed. The percent area occupied (%AO) of CA, pTau, and NFT was calculated. Pairwise comparisons and regression modeling were used to analyze the influence of age, pTau %AO, and genetic risk on %AO by CA in each region, separately in donors with AD and unaffected donors. Results CA %AO was significantly higher in the CA3 region compared to CA1 in both groups. A significant negative correlation of CA %AO with both pTau %AO and neurofibrillary tangle %AO in the CA3 region of AD brain donors was found. Regression analysis in the CA3 region revealed a significant negative association between CA with both pTau and age.ConclusionWe found an increase of CA in the CA3 region, compared to CA1 region, in AD and unaffected donors. This may suggest that the CA3 region is a hub for waste removal. Additionally, the negative correlation between %AO by CA and NFT in the CA3 region of the hippocampus in donors with AD suggests CA could play a role in AD pathologic progression by influencing tau clearance

Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutaneous procedure may lead to new strategies in prevention of type 1 diabetes in humans