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Department of Pharmacology, Centre for Molecular Medicine, Conway Institute of Biomedical and Biomolecular Research University College Dublin Surface Engineering Group, AMS, Department of Mechanical Engineering. University College Dublin .Initial contact between a biological environment and a biomaterial ultimately decides the in vivo performance of the material. Therefore, adhesion of the surrounding cellular tissue is important for the success of a biomaterial. Surface roughness of the biomaterial is one characteristic that can be varied and its effect on cellular adhesion monitored. Resulting changes in water contact angle have been shown to alter adhesive characteristics of a surface. Five different grades of silicon carbide SiC ; sandpaper and 15m diamond polishing powder were used to prepare polystyrene specimens with varying degrees of surface roughness Ra 2.37, 1.16, 0.87, m ; . A control specimen of untreated tissue grade polystyrene was also used in this study Ra 0.005 m ; . The surface roughness was measured by optical profilometry. The water contact angle of the roughened surfaces was in the range 86o to 127o, while the control specimen had a water contact angle of 73o at 37oC. We are in the process of examining the adhesion and growth response of cultured human tumour cells seeded onto these different surfaces, along with assessment of cellular morphology and cytoskeletal organisation. In this way, we hope to provide a useful insight into the influence of surface roughness on cellular phenotype. Funding is acknowledged from Science Foundation Ireland, for example, amaryl for diabetes.
Canadian Guidelines on Sexually Transmitted Infections, 2006 Edition. Public Health Agency of Canada, 2006. Reproduced with the permission of the Minister of Public Works and Government Services Canada, 2006.
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Perhaps what is most striking in Soranus' instructions is his emphasis on cleanliness. He insisted that midwives cut their fingernails and wash their hands in hot oil.20 It is rather revealing and characteristic of the time that he had to specify that this olive oil should not have been previously used in cooking. The mother's vagina should be washed with hot water, and the cloths, compresses, and sponges should also be clean.20 Infection following childbirth has always been a major cause of death. Thus, Soranus' insistence that midwives wash their hands and use clean cloths must have helped in reducing the infection rate. These basic sanitary measures seem only natural to us now, but unfortunately, physicians of later centuries did not always heed Soranus' measures. While most women gave birth at home, the spread of diseases between patients was not a public health issue but it became of fundamental importance with the establishment of maternity wards in hospitals. When in 1847 the Hungarian physician Ignaz Semmelweiss instituted that doctors wash their hands and change their clothes when going from an autopsy to the delivery room, he was criticized and ridiculed by many of his contemporaries who protested that they were gentlemen, and thus their hands were clean.17 Soranus regarded obstetrics as an art, and said that the ideal midwife ".must be literate in order to be able to comprehend the art through theory too".22 Amongst other qualities, she must be calm, have a good memory, be dedicated, quiet, respectable, and strong, and have long, soft, slim fingers. Indeed, she must be an exceptional woman, for as Soranus explains, "a woman who wishes to acquire such vast knowledge needs manly patience".22 If there are complications in the birth, the ideal midwife can make a diagnosis, and based on her knowledge of dietary, surgical, and medical treatments, she can prescribe accordingly.22 At times, Soranus' midwife sounds more like a heroine: "she will be unperturbed, unafraid in danger, able to state clearly the reasons for her measures, she will bring reassurance to her patients, and be sympathetic."22 He writes with equal eloquence about what a midwife should not do. For example, it is not necessary that the midwife be young or have children of her own, but she must not be prone to gossip, superstition, greed, or alcohol, because this would endanger her patients.22 Five hundred years before Soranus, Hippocrates described several diseases and complications of pregnancy. Some of these diseases were associated with the smoothness of the uterus, and bleeding during pregnancy.12 Hippocrates emphasized the importance of accurate history taking several times when discussing gynecology.12 His list of causes of miscarriage is a comprehensive one, which with some paraphrasing would stand up to scrutiny even today: There are also many other dangers by which embryos are aborted; if, for example, a pregnant woman is sick and weak, and if she picks up a burden with all her bodily strength, or if she is beaten, or leaps into the air, or goes without food, or has a fainting spell, or takes too much or too little nourishment, or becomes frightened and scared, or shouts violently. Nurture is a cause of miscarriage, and so is an excessive drink.12 Evidently, foetal alcohol syndrome is not just a modern phenomenon and amphetamine.
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INVITED BOOK CHAPTERS Jeffrey A. Rumbaugh. "Therapies for the Neurological Complications of HIV Infection." In: Johnston, Michael, editor. Principles of Drug Therapy in Neurology. New York, NY: Oxford University Press 2007 ; , in press. Jeffrey A. Rumbaugh and Avindra Nath. "Neuronal Cell Death and Inflammation." In: Haddad, John J., editor. Encyclopedic Reference of Neuroscience. Heidelberg, Germany: SpringerVerlag 2006 ; , in press. Jeffrey A. Rumbaugh and Avindra Nath. "Substance Use Disorders and NeuroAIDS in the HAART Era." In: Goodkin, Karl, editor. The Spectrum of NeuroAIDS Disorders: Pathophysiology, Diagnosis, and Treatment. ASM Press 2005 ; , in press. Jeffrey A. Rumbaugh and Avindra Nath. "Approach to the Patient with a CSF Pleocytosis." In: Irani, David N., editor. Cerebrospinal Fluid in Diseases of the Nervous System. Burlington, MA: Elsevier Inc. 2005 ; , in press. CURRENT EXTRAMURAL RESEARCH SPONSORSHIP Principal Investigator: Jeffrey A. Rumbaugh Mentors: Avindra Nath, Katherine Conant Grant Number: 1 K08 MH07238901 Title: Interaction of HIV Tat and MMP in HIV Neuropathogenesis Sponsor: National Institute of Mental Health Dates: July 2004 to June 2009 Effort: 90% Amount: $50, 000 year for direct research support Description: The aim of this project is to explore the molecular mechanisms and interactions of human and viral factors as they relate to development of neurodegeneration in patients with HIV dementia. In the initial phase of the project, we will utilize a human neuronal cell culture system to investigate the modulation of neuronal toxicity by the interaction of human MMPs with the HIV protein, Tat. We will then use a transgenic murine model system to further explore these interactions in vivo. Finally, we will utilize the framework provided by TatMMP interactions to identify neuroprotective agents which may be clinically useful for the treatment of HIV dementia. This basic research will not only advance clinical medicine through its therapeutic implications for many of the neurological complications of HIV disease but may have implications for understanding the pathophysiology of other viral encephalitides and other dementias as well. PENDING GRANT APPLICATIONS Principal Investigator: Jeffrey A. Rumbaugh CoInvestigators: Robert Cotter, Wenxue Li Title: Novel Host Defense Mechanisms in the Neuropathogenesis of HIV Infection Sponsor: National Institutes of Health, R01 Dates: July 2007 to June 2012 Effort: 50% Amount: $250, 000 year for direct research support and aricept.
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Veronique L Roger, Margaret M Redfield, Susan A Weston, Ryan A Meverden, Steven J Jacobsen; Mayo Clinic, Rochester, MN Heart failure HF ; has been designated as an emerging epidemic of unquestionable clinical and public health importance but it has yet to be fully investigated. Specifically, data on survival in well-characterized, population-based cohorts are scarce and there is limited information on secular trends in survival after incident HF. This study tested the hypothesis that survival after the onset of HF improved over time. Methods: ICD 9 codes 428 HF ; , 425 cardiomyopathy ; , 429.3 cardiomegaly ; and 514 pulmonary congestion ; were used to assemble a populationbased cohort of cases of incident HF, which were validated using the Framingham criteria. Follow- up, which was complete for death, was obtained by review of the entire medical record and the indices of the Rochester Epidemiology Project. Results: Between 1979 and 1998, 3944 cases of incident validated HF 56 % women; mean age 75 14 years ; were identified in Olmsted County. Overall, 5-yr age adjusted survival improved from 59% in 1979 83 to 48% in 1994 98. However, there were large age and sex differences in the degree of improvement in survival p 0.001 for year by age and year by sex interactions ; as shown in the table presenting relative risks 95%CI ; of death after onset of HF adjusted for age. Conclusion: Survival after incident HF improved over time, with however, marked age and sex disparities. This suggests that, even if lead-time bias or treatment effectiveness play a role in the improvement in survival, these do not apply equally across age and sex. This underscores the need for additional studies to elucidate the underlying mechanisms of the improvement in heart failure survival.
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J int med res 2003; 31 6 ; : 503-508 upregulation of cardiac ghrelin mrna in leptin-deficient and leptin receptor-deficient mice with viral myocarditis t kanda 1 , t takahashi 2 , t itoh 3 , k kusaka 4 , j yamakawa 5 , s kudo 6 , t takeda 7 , h tsugawa 8 , n takekoshi 9 1, 2, department of general medicine and 6, 7, 8, department of cardiology, kanazawa medical university, ishikawa, japan expression of cardiac and gastric ghrelin messenger m ; rna, together with heart and body weights, were measured in leptin-deficient db ; and leptin receptor-deficient db ; mice with heart failure induced by viral myocarditis.
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Officer or director of a public company or appearing before the SEC as an accountant and agreed to disgorge a portion of his compensation related to the allegedly inflated revenue reports. In the criminal action, Marks pled guilty and agreed to pay a $65, 000 fine but was not faced with the prospect of any prison time. * * * Defendants-Appellees Respond to SEC's Argument that Participation in "Scheme To Defraud" Establishes Primary Liability for Misrepresentation Under Section 10 b ; Simpson, et al. v. Homestore , Inc., et al., No. 04-55665 9th Cir. ; see document section, infra, page 897 ; As described in Vol. 18 Nov. Dec. 2004 ; , currently pending before the Ninth Circuit is an appeal in which the definitions of primary and secondary liability, and aiding and abetting, under Section 10 b ; of the 1934 Securities Exchange Act and Rule 10b-5 are at issue. The case, Simpson, et al. v. Homestore , Inc., et al., No. 04-55665 9th Cir. ; , involves allegations that third party businesses who allegedly engaged in "barter" or "roundtrip" transactions with Homestore should be held liable for securities fraud as primary violators with respect to Homestore's fraudulent accounting for those transactions. In her March 7, 2003 opinion dismissing the claims, U.S. District Judge Marsha J. Pechman sitting in the Central District of California as a visiting judge ; held that the plaintiff, the California State Teachers' Retirement System, had alleged private aiding and abetting claims for securities fraud, which were prohibited by Central Bank of Denver N.A. v. First Interstate Bank of Denver N.A., 511 U.S. 164 1994 ; . See In re Homestore Sec. Litig., 252 F. Supp. 2d 1018 C.D. Cal. 2003 ; . On appeal, the SEC as amicus curiae argued that the defendants-appellees should be held primarily liable under Section 10 b ; and Rule 10b-5 based on their alleged participation in a "scheme to defraud" Homestore's shareholders. The SEC's amicus brief, which was reproduced in its entirety in Vol. 18 of the Reporter, argued that the appropriate test.
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MATERIALS AND METHODS Agents. Fifty-two dihydroxyisoflavone and trihydroxydeoxybenzoin derivatives were synthesized by the Romark Center for Drug Discovery at University of Liverpool, Liverpool, United Kingdom Table 1 and Fig. 1 ; . Their inhibitory activities on control poly Glu-Ala-Tyr ; phosphorylation were tested using a purified A-431 cell membrane preparation as the human EGF TK source 9 ; by reference to the standard compound PD 153035 CEREP, La Celle l'Evescault, France; data not shown ; . Paromomycin PRM ; was purchased from Sigma, St Louis, Mo. Nitazoxanide NTZ ; , a 2-acetyloxy-N-[ 5-nitro-2-thiazolyl ; ] benzamide, was obtained from Romark Laboratories, Tampa, Fla. For in vitro studies, test agents were solubilized in 100% dimethyl sulfoxide DMSO ; and added to culture wells flasks at final concentrations ranging from 1 to 10 ml, leading to a final DMSO concentration in culture of 0.1% vol vol ; . The same concentration of DMSO was added to cultures with no added agent. For animal gavage, powder formulations of the new synthetic agents PRM and NTZ were suspended in 5% carboxymethylcellulose water. Host cell lines. BM cells originally obtained from peripheral blood monocytes of a 6-year-old Guernsey cow a kind gift from David S. Lindsay, VirginiaMaryland Regional College of Veterinary Medicine, Va. ; were grown in RPMI 1640 medium GIBCO BRL, Gaithersburg, Md. ; supplemented with 2% vol vol ; heat-inactivated fetal calf serum FCS ; , 100 U of penicillin G ml, and 100 g of streptomycin ml. Human colonic epithelial HCT-8 cells CCL 244, passages 42 to 62; obtained from the American Type Culture Collection, Rockville, Md. ; were maintained in RPMI 1640 medium supplemented with 5% FCS, 1% nonessential amino acids, 100 U of penicillin G ml, and 100 g of streptomycin ml in 75-cm2 Falcon flasks, and the medium was changed every second to third day. Evaluation of host cell toxicity of agents. Flat-bottomed 96-well microtiter plates were seeded with BM or HCT-8 cells, and resulting monolayers were used to determine the cytotoxic effects of the test agents. Each agent dilution was examined in triplicate. Cell death due to toxicity was determined using a nitroblue tetrazolium chloride monohydrate reduction assay CellTiter 96 AQueous nonradioactive cell proliferation assay; Promega Corp., Madison, Wis. ; . Decreases in the optical density at 450 nm OD450 ; were expressed as percentages of the OD450 value in agent-free control cultures. Origin of parasites. Cryptosporidium parvum oocysts bovine genotype 2 ; were purified from feces obtained from calves experimentally infected with an isolate maintained by R. Mancassola and M. Naciri, Laboratoire de Pathologie Aviaire, Institut National de Recherche Agronomique, Nouzilly, France. Feces stored in a 2.5% K2Cr2O7 solution for less than 3 months were layered on a discontinuous sucrose density gradient densities, 1.045 and 1.090 ; , and isolated oocysts were bleached before excystation and cell culture infection. Sarcocystis neurona strain SnSO-1 merozoites originated from a Southern sea otter, and Neospora caninum merozoites of the NC-1 strain were kind gifts of David S. Lindsay and were handled as previously reported 15, 27 ; . Assessment of the inhibitory activities of agents on Neospora caninum and Sarcocystis neurona in vitro development. Cells were resuspended in 25-cm2 culture flasks or in 6-well culture plates containing culture medium. They were incubated for 1 to 2 days. When the monolayer was 80% confluent, each culture recipient was inoculated with Sarcocystis neurona or Neospora caninum merozoites harvested from infected BM cell cultures which were detached from the plastic growth surface by using a rubber cell scraper and passed through a 30-gauge needle attached to a syringe to rupture host cells. As previously described, this procedure resulted in cell monolayer infection, which was microscopically checked 16, 26 ; . Parasites were harvested by centrifugation 10 min, 1, 800 g, 4 to 10C ; and resuspended in RPMI 1640 medium at room temperature. Merozoites were counted using a hemacytometer, and each culture flask.
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[19] In order to study the performance of the search and to explore the resolution of the obtained models we conducted synthetic tests. Data were generated for the same source and receiver geometry same station spacing etc. ; as in our experiment, and parameter settings as shown in Table 3. We added random time shifts of at most 0.005 s and random noise maximum signal-to-noise ratio of 5 ; to the synthetics, which we then inverted in the same way as the real data. Synthetic time series are shown in Figure 3. [20] We inverted for four free parameters: waveguide width w, velocity ratio vs, 2 vs, 1, host rock velocities vs, 1 and vs, 3 which we set identical except for a small perturbation to avoid unrealistic symmetry effects in the syn1 thetics ; and an overall attenuation factor Q1 Q1 Q1 The lateral source position was set fix to one interface between waveguide and host rock. Furthermore, the position of the receiver observing the largest guided wave amplitude was fixed to the center of the waveguide. [21] Figures 4a 4d shows values of the fitting function F ; of all in the GA run tested models as a function of the four free parameters. In our implementation of GA search we ran 300 generations approximately 15, 000 tested models ; until we achieved a satisfactory fit and a broad sampling of the parameter space. As expected, the GA search reveals a suite of models with an acceptable fit F 0.85 ; . The best tested model reaches F 0.89, which is the same value as.
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