Transcriptional and Post-Transcriptional Control of Therapeutic Gene Expression during Disease Activity

PhDRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which predominantly affects the synovial joints. Local gene therapy represents an approach to produce therapeuticmolecules (i.e. soluble TNF receptor (sTNFR)-Fc and interleukin-1 receptor antagonist (IL-1Ra)) directly in arthritic joints. Gene therapy could be designed to link the level of therapeutic gene expression directly to disease activity, through the use of transcriptional and posttranscriptional regulatory elements. The experiments in this thesis describe the construction of multi-responsive, composite synthetic promoters, comprised of the binding sites for an array of transcription factors activated in arthritic joints. Optimal spatial arrangements of binding sites in relation to each other and to the TATA box were determined by Assembly PCR cloning and the functionality of the resulting synthetic promoters revealed additive or synergistic induction of luciferase reporter gene expression in response to combined stimulation. Candidate synthetic promoters were cloned into a lentiviral vector between insulator elements and displayed significantly enhanced induction, in excess of 1,500 fold in response to combined stimulation. Inflammation-specific activation of lentiviral synthetic promoters was confirmed in a carrageenan-induced paw inflammation mouse model, which demonstrated the strong correlation between local luciferase gene expression and paw inflammation. Post-transcriptional gene regulation was also investigated by exploiting the differential expression of endogenous miR-23b during inflammation. Insertion of miR-23b target sites into the 3’UTR of the luciferase gene subjected luciferase mRNA to regulation by miR-23b. Experiments demonstrated that high basal gene expression driven by constitutive and inducible promoters was significantly downregulated by miR-23b without significantly impairing high gene expression upon stimulation. Overall, the experiments in this thesis have confirmed the induction of inflammation-specific gene expression, regulated by inflammationresponsive endogenous transcriptional and post-transcriptional elements.Medical Research Council (MRC) funding - MRes and PhD studies during four year MRes/PhD Studentship. British Pharmacological Society (BPS) for additional funding

Understanding multilevel barriers to childhood vaccination uptake among Internally Displaced Populations (IDPs) in Mogadishu, Somalia: a qualitative study

BACKGROUND: Disparities in vaccination coverage exist in Somalia with Internally Displaced Persons (IDPs) being among the groups with the lowest coverage. We implemented an adapted Participatory Learning and Action (PLA) intervention, which focused on routine vaccinations among displaced populations living in Mogadishu IDP camps. The intervention was successful in improving maternal knowledge and vaccination coverage but unsuccessful in improving timely vaccination. We conducted a qualitative study to understand this result and analyze the multi-level barriers to routine childhood immunization uptake. METHOD: In this qualitative study we used observation data from 40 PLA group discussions with female caregivers and purposively sampled nine vaccination service providers and six policy makers for interview. We also reviewed national-level vaccine policy documents and assessed the quality of health facilities in the study area. We used the socioecological framework to structure our analysis and analyzed the data in NVivo. RESULTS: The barriers to childhood vaccination among IDPs at the individual level were fear due to lack of knowledge, mistrust of vaccines, concerns about side effects and misinformation; opportunity costs; and costs of transportation. At the interpersonal level, family members played an important role as did the extent of decision-making autonomy. Community factors such as cultural practices, gender roles, and household evictions influenced vaccination. Organizational issues at health facilities such as waiting times, vaccine stock-outs, distance to the facility, language differences, and hesitancy of health workers to open multi-dose vials affected vaccination. At the policy level, confusion about the eligible age for routine vaccination and age restrictions for catch-up vaccination and certain antigens such as BCG were important barriers. CONCLUSION: Complex and interrelated factors affect childhood vaccination uptake among IDPs in Somalia. Interventions that address multiple barriers simultaneously will have the greatest impact given the complex nature of vulnerabilities in this population. There is a need to strengthen the health system and connect it with existing community structures to increase demand for services. Our research highlights the importance of formative research before implementing interventions. Further research on the integration of health service strengthening with PLA to improve childhood vaccination among IDPs is recommended. TRIAL REGISTRATION NUMBER: ISRCTN-83,172,390. Date of registration: 03/08/2021

SJUKSKÖTERSKORS ERFARENHETER AV ATT VÅRDA PATIENTER I LIVETS SLUTSKEDE : En litteraturstudie om sjuksköterskors erfarenheter

Bakgrund: Palliativ vård fokuserar på att lindra symtom och främja livskvaliteten. I palliativ vård finns det en tidigare fas och en sen fas. I detta examensarbete inkluderas den sena fasen. Syfte: Att beskriva sjuksköterskors erfarenheter av att vårda patienter i livets slutskede. Metod: Metoden var en systematisk litteraturstudie, enligt Evans med fokus på sjuksköterskors erfarenheter av att ta hand om patienter i livets slutskede. Resultat: Resultatet visade att mötet mellan sjuksköterskor och patienter i livets slutskede hade stor betydelse. Vidare beskrevs vikten av en god vårdrelation. Resultat beskrev att det var viktigt att patienter var delaktiga i vården för att kunna individanpassa och bevara patienters integritet. Resultatet visade även det var viktigt att involvera anhöriga i vården. Sjuksköterskorna betonade även vikten av att dela erfarenhet och ge stöd till kollegor. Slutsats: Resultatet visade att mötet mellan sjuksköterskorna och patienter i livets slutskede var av stor betydelse. Vården av dessa patienter krävde ett stort ansvar för att upprätthålla en god vårdrelation. Vidare betonas vikten av att inkludera patienter i vården samt ge adekvat stöd och kommunikation med anhöriga. Resultatet understryker även betydelsen av effektiv kommunikation och stöd från erfarna kollegor. Dessutom underlättade en positiv arbetsmiljö att stressnivån sjönk och det blev därmed lättare att hantera utmanande situationer inom palliativ vård.

The Activism of First Generation Somali Canadian Women within a Neoliberal Multicultural State

This thesis aims to explore the activism of first generation Somali Canadian Women (FGSCWA). It specifically asks 1) how do Somali women activists engage, contest and modify existing social relations within their community and mainstream society to foster anti-racist, anti-Islamaphobic feminist spaces; 2) in what ways does their activism challenge the systematic racism and Islamaphobia that is explicitly and implicitly imbedded in Canadian institutions and social relations and; 3) how has their activism and advocacy challenged the normative discourse of neoliberal multiculturalism, while simultaneously contesting gender norms and cultural dogma within the Somali community. This study combines two theoretical approaches to understand issues of citizenship, boundaries of Blackness and Muslim identity, power, representation and knowledge production in relation to Somali women activists. Working within a post-colonial and Black feminist framework, this research paper utilizes the in-depth interviews I conducted with eight Somali women activists, narrating their perspectives and lived experiences.M.A.2018-05-10 00:00:0

HIV infected patients' experiences in the meeting with the nurse : A literature review on HIV infected patients' experiences

Bakgrund. HIV är förkortningen av Humman Immunbrist Virus medan AIDS förkortningen är Acquried Immune Deficieny Syndrome. HIV upptäcktes först i USA under 1980-talet. De senaste 20 åren har 750 000 dött av HIV/AIDS i USA. HIV ingår i familjen retrovirus och har förmåga att omvandla sina RNA arvanslag till DNA kopia med hjälp ett enzym. En obehandlad HIV utvecklas till AIDS som är slutstadiet. Det beräknas att ca 38,7 miljoner människor lever med HIV idag världen över. HIV/AIDS smittar främst via oskyddad sex, kontakt med infekterade kroppsvätskor och stick-och skärskador. Att få en HIV-diagnos är svårt och kan leda till svår psykisk ohälsa på grund av HIV-relaterade stigma. Syfte: Att belysa hur HIV- och/eller AIDS-smittade personer upplever mötet med sjuksköterskan i USA. Metod: Studien är baserad på nio kvalitativa vetenskapliga artiklar. Artiklarna är bearbetade och granskade enligt Fribergs granskningsmall, (2018). Databaserna som användes vid sökningen är Cinahl och PubMed. Resultat: HIV/AIDS-smittade patienter i USA upplevde båda positiva och negativa upplevelser i mötet med sjuksköterskan. Resultatet presenteras i följande kategorier: Behovet av stöd vid diagnostiseringen, Respekt och Medmänsklighet, Brist på respekt och ignorans, Stigmatiserande och Förtroende för vårdgivare. Slutsats: I resultatet framkommer att HIV och/eller AIDS-smittade personer som upplever mötet med sjuksköterskan som negativt är överrepresenterade. Detta tyder på att sjuksköterskor behöver utbildning och kunskap för att bli bättre i mötet med dessa patienter och erbjuda en god och värdig vård.Background: HIV (Human Immunodeficiency Virus) was detected in the United States during 1980s and over 750 000 have died for the last 20 years because of HIV. The Virus is included in the retroviruses family and it has the ability to convert it’s RNA inheritance to DNA by using an enzyme. An untreated HIV makes it harder for the body to fight back the virus and this developing can end the life. Today it’s estimated that more than 38,7 million people worldwide live with HIV. The virus is mainly transmitted through unprotected sex, contact with infected body fluids and cutting injuries. Purpose: The purpose of this study was to investigate how HIV/AIDS infected people experience during the meeting with the nurses in the United States. Method: The method used in the study was based on 9 qualitative scientific articles. Result: The result of this study shows that the infected persons of the virus, experience both negatively and positively feelings during the meeting with the nurses. Conclusion: The result shows that persons experience negatively feelings is higher than the others are. It’s obvious that the nurses in the United States need more knowledge and practice about how to take care and response for the HIV effected persons

Muslim Women on the Margin: On Whose Authority Does Islamic Knowledge Rest

This paper will examine Muslim women’s engagement in Islamic scholarship by reviewing the foundational source of Islamic knowledge while referencing Somali female activists I interviewed in my 2017 published thesis. In particular, Somali women’s active participation within the realm of Islamic scholarship in the diaspora will be reviewed, including how the contribution of religious knowledge has enhanced Somali women’s faith and their active leadership in their communities. Moreover, I will analyze the orthodoxy limitation that has attempted to erase their scholarship

Somalinaisten synnytyskokemus - teemahaastattelu

Opinnäytetyömme tarkoituksena on kuvailla Suomessa asuvien somalinaisten synnytyskokemuksia. Tavoitteenamme on tuoda esille tietoa haastattelun avulla somalinaisten synnytyskokemuksista ja hyödyntää tätä tietoa synnytyksen hoidon opetuksen kehittämisessä, sekä kätilötutkinnon kehittämisen tukena. Opinnäytetyömme on osa Metropolian Ammattikorkeakoulun kätilötyöopintoja. Opinnäytetyön suunnitteluvaihe toteutetaan syksyllä vuonna 2020 ja toteutus- ja raportointivaihe siirtyy vuoden 2021 keväälle. Opinnäytetyö toteutettiin kvalitatiivisena eli laadullisena tutkimuksena. Haastattelumuotona oli puolistrukturoitu teemahaastattelu, joka toteutettiin yksilöhaastatteluna. Aineistoa kerättiin haastattelemalla kuutta Suomessa synnyttänyttä somalinaista, joiden edellisestä synnytyksestä oli kulunut alle kolme vuotta. Kolme somalinaisista oli syntynyt Somaliassa ja kolme muuta Suomessa. Haastattelun osallistuminen oli vapaaehtoista. Koronapandemian aikana osa haastatteluista toteutettiin etänä ja osa kasvotusten rajoituksia noudattaen. Somalinaiset kokivat synnytyskokemuksiensa olleen myönteisiä, mutta myös haastavia. Synnytyskokemus koettiin haastavana erilaisten siihen vaikuttavien tekijöiden pohjalta. Haastavia tekijöinä olivat muun muassa odotusten ja toiveiden toteutumattomuus, osalla synnytyksen yleinen haastavuus, kivunlievityksen riittämättömyys ja vuorovaikutus kätilön kanssa kuvailtiin jossain määrin haasteellisena

Understanding multilevel barriers to childhood vaccination uptake among Internally Displaced Populations (IDPs) in Mogadishu, Somalia: a qualitative study

Abstract Background Disparities in vaccination coverage exist in Somalia with Internally Displaced Persons (IDPs) being among the groups with the lowest coverage. We implemented an adapted Participatory Learning and Action (PLA) intervention, which focused on routine vaccinations among displaced populations living in Mogadishu IDP camps. The intervention was successful in improving maternal knowledge and vaccination coverage but unsuccessful in improving timely vaccination. We conducted a qualitative study to understand this result and analyze the multi-level barriers to routine childhood immunization uptake. Method In this qualitative study we used observation data from 40 PLA group discussions with female caregivers and purposively sampled nine vaccination service providers and six policy makers for interview. We also reviewed national-level vaccine policy documents and assessed the quality of health facilities in the study area. We used the socioecological framework to structure our analysis and analyzed the data in NVivo. Results The barriers to childhood vaccination among IDPs at the individual level were fear due to lack of knowledge, mistrust of vaccines, concerns about side effects and misinformation; opportunity costs; and costs of transportation. At the interpersonal level, family members played an important role as did the extent of decision-making autonomy. Community factors such as cultural practices, gender roles, and household evictions influenced vaccination. Organizational issues at health facilities such as waiting times, vaccine stock-outs, distance to the facility, language differences, and hesitancy of health workers to open multi-dose vials affected vaccination. At the policy level, confusion about the eligible age for routine vaccination and age restrictions for catch-up vaccination and certain antigens such as BCG were important barriers. Conclusion Complex and interrelated factors affect childhood vaccination uptake among IDPs in Somalia. Interventions that address multiple barriers simultaneously will have the greatest impact given the complex nature of vulnerabilities in this population. There is a need to strengthen the health system and connect it with existing community structures to increase demand for services. Our research highlights the importance of formative research before implementing interventions. Further research on the integration of health service strengthening with PLA to improve childhood vaccination among IDPs is recommended. Trial registration number ISRCTN-83,172,390. Date of registration: 03/08/2021