Methods of studying the interaction between fish viruses with inanimate surfaces were developed and used to explore several variables. Viral hemorrhagic septicemia virus (VHSV) was used as the model virus. The EPC cell line, which is now known to be from Fathead Minnow, was used to detect the virus through the development of cytopathic effect (CPE); this allowed virus levels to be titrated and expressed as tissue culture infectious dose (TCID50). The labour and tedium of scoring hundreds of wells for CPE was overcome through the use of the fluorescent indicator dye, Alamar Blue, which is reduced by living cells and not by dead cells to yield a fluorescent product that can be measured as relative fluorescence units (RFUs) with a fluorescent microwell plate reader. Microsoft Excel 2007 was used to compare RFU values of wells and to create a scoring template in the computer program that allowed for easy summation of the total number of wells with infectious virus. With this system and as well as with conventional scoring, surface-virus interactions were studied in the following general way. Surfaces were incubated with a solution (L-15 with 2% fetal bovine serum or FBS) of virus, rinsed, and then incubated under various conditions, either wet or dry, before being evaluated for infectious virus. The transfer of viruses through their elution from surfaces is termed elution transfer (ET) and was investigated in two ways: agitated elution and static elution. Agitated elution was done through the repeated action of pipetting up and down on either glass or plastic surfaces with different eluting solutions. The best eluting solution was 2% FBS/L-15 and the worst was tissue culture grade water. Regardless of the eluting solution, no infectious virus could be removed by agitated elution from glass Petri dishes. Static elution was demonstrated through a two-compartment culture system linked by 3.0 m pores. L-15 with 2% FBS eluted VHSV from the surface of the top chamber to infect cells in the bottom chamber and from the surface of the bottom chamber to infect cells in the top chamber. The ability of different objects to carry infectious VHSV to a new culture vessel was investigated in a protocol termed object-associated transfer (OAT). The objects were incubated with VHSV, rinsed, and then incubated wet or dry for various periods before being transferred to EPC cultures. After up to ten days of wet incubation, pieces of glass, fishing line, plastic water bottle, and pop can were able to transfer infectious virus. In contrast, when the same objects were incubated dry, they were able to transfer VHSV after only one day of drying. Fishing hooks kept wet for a day were able to transfer VHSV but dry hooks had no capacity to transfer infectious virus. A third experimental protocol was used to detect infectious viruses on surfaces and involves the surface to cell transfer (SCT) of viruses. For this protocol, EPC cells were plated directly onto plastic or glass surfaces that previously had been exposed to virus, rinsed, and incubated dry or wet at various temperatures for up to 15 days. After 15 days being kept dry at 4 °C, infectious VHSV was still found to be present on both glass and plastic surfaces. At 14 °C and room temperature, the virus was found to survive longer on plastic than on glass, and at 26 °C both surfaces retained infectious VHSV for only one day of being dry. Survival time on plastic surfaces at different temperatures was compared for wet and dry incubation. VHSV kept on plastic surface in a dry state was more susceptible to temperature inactivation, with inactivation of the virus being detected clearly after 1 day 37 °C, 10 days at 26 °C, and 15 days at room temperature.

Methods of studying the interaction between fish viruses with inanimate surfaces were developed and used to explore several variables. Viral hemorrhagic septicemia virus (VHSV) was used as the model virus. The EPC cell line, which is now known to be from Fathead Minnow, was used to detect the virus through the development of cytopathic effect (CPE); this allowed virus levels to be titrated and expressed as tissue culture infectious dose (TCID50). The labour and tedium of scoring hundreds of wells for CPE was overcome through the use of the fluorescent indicator dye, Alamar Blue, which is reduced by living cells and not by dead cells to yield a fluorescent product that can be measured as relative fluorescence units (RFUs) with a fluorescent microwell plate reader. Microsoft Excel 2007 was used to compare RFU values of wells and to create a scoring template in the computer program that allowed for easy summation of the total number of wells with infectious virus. With this system and as well as with conventional scoring, surface-virus interactions were studied in the following general way. Surfaces were incubated with a solution (L-15 with 2% fetal bovine serum or FBS) of virus, rinsed, and then incubated under various conditions, either wet or dry, before being evaluated for infectious virus. The transfer of viruses through their elution from surfaces is termed elution transfer (ET) and was investigated in two ways: agitated elution and static elution. Agitated elution was done through the repeated action of pipetting up and down on either glass or plastic surfaces with different eluting solutions. The best eluting solution was 2% FBS/L-15 and the worst was tissue culture grade water. Regardless of the eluting solution, no infectious virus could be removed by agitated elution from glass Petri dishes. Static elution was demonstrated through a two-compartment culture system linked by 3.0 m pores. L-15 with 2% FBS eluted VHSV from the surface of the top chamber to infect cells in the bottom chamber and from the surface of the bottom chamber to infect cells in the top chamber. The ability of different objects to carry infectious VHSV to a new culture vessel was investigated in a protocol termed object-associated transfer (OAT). The objects were incubated with VHSV, rinsed, and then incubated wet or dry for various periods before being transferred to EPC cultures. After up to ten days of wet incubation, pieces of glass, fishing line, plastic water bottle, and pop can were able to transfer infectious virus. In contrast, when the same objects were incubated dry, they were able to transfer VHSV after only one day of drying. Fishing hooks kept wet for a day were able to transfer VHSV but dry hooks had no capacity to transfer infectious virus. A third experimental protocol was used to detect infectious viruses on surfaces and involves the surface to cell transfer (SCT) of viruses. For this protocol, EPC cells were plated directly onto plastic or glass surfaces that previously had been exposed to virus, rinsed, and incubated dry or wet at various temperatures for up to 15 days. After 15 days being kept dry at 4 °C, infectious VHSV was still found to be present on both glass and plastic surfaces. At 14 °C and room temperature, the virus was found to survive longer on plastic than on glass, and at 26 °C both surfaces retained infectious VHSV for only one day of being dry. Survival time on plastic surfaces at different temperatures was compared for wet and dry incubation. VHSV kept on plastic surface in a dry state was more susceptible to temperature inactivation, with inactivation of the virus being detected clearly after 1 day 37 °C, 10 days at 26 °C, and 15 days at room temperature.

Stroke is a devastating, neurological dysfunction due to brain blood supply disturbance. It is responsible for increasingly high rate of mortality and disability worldwide. This thesis comprises two original studies involving 868 patients at risk of ischemic stroke and/or hemorrhagic stroke. The first study investigated aspirin’s effect among patients with intracranial hemorrhage. Unlike Caucasians which hemorrhagic strokes account for 10-15% of all strokes; in Chinese, intracranial hemorrhages strike up to 35%. After such, anti-platelet agent like aspirin is often avoided for fear of recurrent intracranial hemorrhages, despite compelling indications. However, clinical data is limited. In this single-centered observational study, we included 440 consecutive Chinese patients with a first spontaneous intracranial hemorrhage surviving the first month performed during 1996-2010. 56 patients (12.7%) of these 440 patients were prescribed aspirin after intracranial hemorrhage (312 patient-aspirin years). After a mean follow-up of 62.2 ± 1.8 months, 47 patients had recurrent intracranial hemorrhage(10.7%, 20.6 per 1,000 patient years). Patients prescribed aspirin did not have higher risk of recurrent intracranial hemorrhage compared with those without (22.7 per 1,000 patient-aspirin years vs. 22.4 per 1,000 patient years, p=0.70). Multivariate analysis identified age > 60 years and hypertension as independent predictors for recurrent intracranial hemorrhage. In a subgroup analysis: the incidence of combined vascular events including recurrent intracranial hemorrhage, ischemic stroke, and acute coronary syndrome was statistically lower in patients prescribed aspirin than without (52.4 per 1,000 patient-aspirin years, vs. 112.8 per 1,000 patient-years, p=0.04). Implications of the results: despite having a substantial risk for recurrent intracranial hemorrhage, post-intracranial hemorrhage ones are at risk for thrombotic vascular events and management goal should thus focus on ameliorating overall cardiovascular risk instead of preventing recurrent intracranial hemorrhage. Hence, thrombo-prophylaxis should still be considered. The second study investigated the relation between premature atrial complexes and new-onset atrial fibrillation together with other cardiovascular events. Premature atrial complexes though taken as benign phenomenon, are common in patients with underlying conditions such as coronary heart disease, chronic rheumatic heart disease. While prompt management of atrial fibrillation may prevent ischemic stroke, atrial fibrillation is often unfound until ischemic stroke occurs. In this study, 428 patients without atrial fibrillation but complained of palpitations, dizziness or syncope were recruited. 107 patients with >100 premature atrial complexes/day were defined to have frequent premature atrial complexes. After a mean follow-up of 6.1 ±1.3 years, 31 patients (29%) with frequent premature atrial complexes developed atrial fibrillation compared with 29 patients (9%) with premature atrial complexes?100/day (p<0.01). Cox regression analysis revealed: frequent premature atrial complexes, age>75 years and coronary artery disease were independent predictors. In secondary endpoint (ischemic stroke, congestive heart failure, and death), patients with frequent premature atrial complexes were more at risk than those without (34.5% vs. 19.3%) (Hazard ratio: 1.95, 95% confidence interval: 1.37-3.50, p=0.001). Cox regression analysis showed: age> 75 years, coronary artery disease and frequent premature atrial complexes were independent predictors. These permit early identification of high risks patients of new atrial fibrillation and other events, thus promoting appropriate preventive treatment. / published_or_final_version / Medicine / Master / Master of Philosophy

Introduction: Recent Ebola epidemic in West Africa have put viral hemorrhagic fever diseases in the spotlight. Uganda has had several outbreaks throughout the years, which have successfully been managed. Nurses’ patient education plays an important role in the work to increase public awareness about viral hemorrhagic fever diseases. Objectives: To assess how nurses at the emergency department educate the patients and relatives about the viral hemorrhagic fever diseases. Methods: An explorative and descriptive qualitative study with qualitative approach have been used. In-depth interviews with 18 open-ended questions have been conducted with nurses in the emergency department. Data was analyzed by qualitative content analysis and analyzed with Peplau’s theory of interpersonal relationship. Results: Through data analysis four categories were developed; Wide variety of educational techniques, Experienced obstacles, How to attain wider audience and Preferable characteristics as an educating nurse. Nurses used many different approaches when educating about viral hemorrhagic fever diseases, often uniquely combined. Lack of time and too unstable patients in the emergency department were seen as the main obstacles to educate. Methods to reach the community and employing a special education-nurse on the ward were suggestions to improve the preventive work against viral hemorrhagic fever diseases. Conclusion: Nurses are aware of the importance of patient education and use the educational methods they believe to be the most effective. However, patients in the emergency department often come in too late and priority should be on preventive measures. Training the nurses in educational techniques and patient education could be a key in decreasing the risk of coming outbreaks. / Bakgrund: Den senaste ebolaepidemin i västafrika har gjort att blödarsjukdomar hamnat i rampljuset. Uganda har genom åren drabbats av flera utbrott som framgångrikt hanterats. Sjuksköterskors patientutbildning spelar en viktig roll i arbetet för att öka allmänhetens medvetenhet om blödarsjudkomar. Syfte: Att undersöka hur sjuksköterskor på akutmottagningen utbildar patienter och anhöriga om blödarsjukdomar. Metod: En explorativoch deskriptiv kvalitativ studie med kvalitativ ansats användes. Sjuksköterskor som arbetar på akutmottagningen har djupintervjuats med 18 öppna frågor. Data har analyserats med en kvalitativ innehållsanalys och analyserats utifrån Peplaus ”interpersonal relationship theory”. Resultat: Genom dataanalysen utvecklades fyra kategorier; Stor variation på utbildningstekniker, Upplevda hinder, Hur man ska nå en bredare publik och Önskvärda egenskaper som utbildande sjuksköterska. Sjuksköterskorna använder många olika metoder för utbilda patienter och anhöriga om blödarsjukdomar, ofta i unika kombinationer. Tidsbrist och alltför instabila patienter på akutmottagningen sågs som de största hindren för att utbilda. Metoder för att nå allmänheten och att anställa en speciell utbildningssjuksköterska på avdelningen var några av förslagen för att förbättra det förebyggande arbetet mot blödarsjukdomar. Slutsats: Sjuksköterskorna är medvetna om vikten av patientutbildning och använder de pedagogiska metoder de anser vara mest effektiva. Då patienterna kommer till akutmottagningen är det dock ofta för sent och preventiva åtgärder borde prioriteras. Att öka sjuksköterskornas kunskap i utbildningstekniker och patientutbildning kan vara en viktig del i det preventiva arbetet för att minska risken för kommande utbrott.

Immune cytokines tumor necrosis factor alpha and type I interferons provide front-line defense against viral infection and are regulated in part by ubiquitin (Ub) and Ub-like molecules. Ubiquitin and Ub-like molecule ISG15 share a conserved C-terminal motif where a terminal glycine residue becomes attached to cellular target proteins. Nairoviruses and arteriviruses contain an ovarian tumor domain-containing protease (OTU protease) that was found to corrupt pathways by removing Ub or ISG15 from target proteins. This broad substrate specificity is unlike mammalian deubiquitinating enzymes, which cannot recognize both substrates. To understand how viral OTU domain-containing proteases remove Ub and ISG15, the crystal structure of the Crimean-Congo Heamorhaggic Fever nairovirus (CCHFV) was determined with Ub to 2.5 Å resolution. A computational model was built of the CCHFV Otu protease bound to ISG15 as well. The CCHFV Otu protease has several structural differences from known OTU proteases, manifesting in its broad substrate recognition capability.

Immune cytokines tumor necrosis factor alpha and type I interferons provide front-line defense against viral infection and are regulated in part by ubiquitin (Ub) and Ub-like molecules. Ubiquitin and Ub-like molecule ISG15 share a conserved C-terminal motif where a terminal glycine residue becomes attached to cellular target proteins. Nairoviruses and arteriviruses contain an ovarian tumor domain-containing protease (OTU protease) that was found to corrupt pathways by removing Ub or ISG15 from target proteins. This broad substrate specificity is unlike mammalian deubiquitinating enzymes, which cannot recognize both substrates. To understand how viral OTU domain-containing proteases remove Ub and ISG15, the crystal structure of the Crimean-Congo Heamorhaggic Fever nairovirus (CCHFV) was determined with Ub to 2.5 Å resolution. A computational model was built of the CCHFV Otu protease bound to ISG15 as well. The CCHFV Otu protease has several structural differences from known OTU proteases, manifesting in its broad substrate recognition capability.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 2005. / Bibliyografya var.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (M.P.H.M.(Primary Health Care Management))--Mahidol University, 2006.

Thesis (Ph. D.)--University of Virginia, 2008. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.