Propofol Directly Increases Tau Phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology

The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications

Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids

Failure or success of African SME’s : a study on UWAZI cooperation in Zanzibar

In the discussions today about Africa’s way out of poverty the main focus has been on SME’s, and there potential to increase the economy. In my thesis I research a network of small scale producers in Zanzibar called UWAZI. The thesis compares the theory of Robertson and Lussier, with UWAZI’s situation in Zanzibar. The two most important factors for success are identified as networks and financing which this thesis is focusing on. The conclusion is that UWAZI needs a better financing programme in order to be successful in the future and if this is implemented there is no reason for them to fail. They have a strong network and cooperation and a good mentor programme linked to the business. This thesis proves that it is possible for a women network to reach a successful enterprise in Africa

Healthy women or risk patients? : Non-attendance in a cervical cancer screening program

Women afflicted with cervical cancer who have the highest morbidity and mortality rates have been the least likely to be screened. The overall aim of this research project was to investigate non-attendance in a cervical cancer screening (CCS) program among women with no registered cervical smear during the previous five years. Both quantitative (I,III) and qualitative methods (II) as well as costeffectiveness analysis (IV) were used in this research project. In Kalmar County women (aged 23-65 years) are invited to CCS every third year. All cervical smears taken both in opportunistic and organised CCS are coordinated in a register called Sympathy. The coverage is 88.4 %. From Sympathy, a random sample of 400 women served as a study group and another 400 women as a control group (III,IV). From the study group, 133 women participated in study I and 14 women in study II. Data was collected by telephone interviews based on a questionnaire (I), qualitative face-to-face interviews (II), questionnaire, promotive efforts and outcome (III), costs and effectiveness (IV). Quantitative data was analysed by descriptive and analytic statistics (I,III), qualitative data was analysed by content analysis. In study IV, cost-effectiveness analysis was used. The women believed that CCS was a good idea for all other women, but tended to refer to various circumstances resulting in their own non-attendance. One of the most common reasons for non-attendance was the feeling of being healthy. The women prioritized family and work commitments, and the invitation to attend CCS was sometimes experienced as a stressful disturbance. The feeling of discomfort was related to the gynaecologic examination, or to health care visits in general (I,II). Of 133 women, 120 could consider having a cervical smear taken and their two most common requirements for doing so were to be assured they would be treated in a friendly way (19%) and to find a suitable time (18%) for having the cervical smear. Fifty women wanted to be helped to have a cervical smear taken. Promotive efforts ranged from making a simple telephone call to arranging an appointment time to a combination of promotive efforts including repeated encounters in order to create a trusting relationship with respect to taking the smear. In the study group, 29.5% (n=118) had a registered cervical smear at follow-up compared to 18.5% (n=74) in the control group, (p&lt;0.001) (III). In the study group, the cost per cervical smear taken was 66.87 €, and in the control group it was 16.62 €. The incremental cost per additional cervical smear taken was 151.36 € (IV). In conclusion, women’s reasons for not attending CCS are complex and are influenced by both present and earlier circumstances. In settings with high coverage, further contact in order to promote women’s attendance at CCS seems to be associated with high costs in relation to the number of additional cervical smears taken.On the day of the defence data the status of article I was: In press; article II: Submitted; article II: Accepted and artile IV: In press.</p

Students´use of reading comprehension strategies : Five students´experiences in the latter part of elementary school

Studien syfte är att utröna högstadieelevers användning av läsförståelsestrategier vid faktabaserade texter. Datamaterialet baseras på fem intervjuer utifrån följande frågor: Vilka läsförståelsestrategier använder sig eleverna av, i vilket syfte använder sig eleverna av läsförståelsestrategierna och är elevernas val av strategier samt syftet med dem medvetna eller omedvetna? Arbetet är en kvalitativ studie som bygger på semistrukturerade och personliga intervjuer med flickor från årskurs åtta som går i samma klass. I denna studie ses läsförståelse ur ett kognitivt perspektiv som lett till att en induktiv analys av datamaterialet skett. Studiens resultat visar att de medverkande eleverna använder sig av flera strategier samt att de kan redogöra för i vilket syfte de använder sig av dem. Eleverna använder sig av någon eller några former av djupare läsförståelsestrategier samt sin metakognitiva förmåga. De är således medvetna om vilka mentala aktiviteter som leder till läsförståelse. Studien visar att det dock finns utrymme för ytterligare strategier att tillämpa utifrån den litteratur som ligger till grund för undersökningen. Detta även med resultaten från senaste PISA-undersökningen i åtanke. För att få en bättre helhetsbild i elevernas användning av läsförståelsestrategier, behandlar studien det stöd som den svenska läroplanen ger lärarna i arbetet kring elevers läsförståelse

Etiska dilemman i samband med vaccination mot HPV

Humant papillomvirus (HPV) är en av de vanligaste sexuellt överförbara infektionerna. HPV kan leda till cellförändringar och cervixcancer hos kvinnor men viruset är även en av orsakerna till anal-, huvud- och halscancer. Flera problemområden har identifierats i samband med att vaccination mot HPV infördes i barnvaccinationsprogrammet. Ett problem är svårigheten att uppnå informerat samtycke till HPV-vaccination. Ur ett jämlikhetsperspektiv är det ett problem att endast flickor erbjuds HPV-vaccinering i barnvaccinationsprogrammet. Genom att endast vaccinera flickor stigmatiseras bilden av flickor som smittbärare. Pojkar har inte tillgång till kostnadsfri vaccinering trots att de är smittbärare av HPV och kan drabbas cancer. Genom att utesluta pojkar från allmänna vaccinationsprogram så diskrimineras sårbara grupper som t.ex. män som har sex med män