Resumo: Há algumas poucas evidências de que danos teciduais causados por parasitas gastrintestinais em ovinos promovem estresse oxidativo, porém os mecanismos que causam o desequilíbrio entre os oxidantes e antioxidantes não estão bem estabelecidos. O presente trabalho objetivou comprovar a hipótese de que o estresse oxidativo ocorre em ovinos infectados por Haemonchus contortus e que este varia com a resistência racial. Para tanto foram investigadas as relações entre o estresse oxidativo causado pela infecção por H. contortus, a carga parasitária, a anemia e a hipoalbuminemia. Para tal, ovinos da raça Suffolk (n=15) e Santa Inês (n=22) foram desverminados e após confirmado a ausência de ovos nas fezes (dia 0), todos animais foram infectados por via oral com 5000 larvas de terceiro estágio (L3) de H. contortus. A quantidade de ovos por grama de fezes (OPG) e a concentração de diferentes marcadores plasmático de estresse oxidativo (peroxidação lipídica, albumina, ácido úrico, bilirrubina total, capacidade antioxidante total, concentração de oxidante total e o índice de estresse oxidativo) foram quantificadas antes (dia 0) e com 28, 32 e 42 dias da infecção experimental, em ambas as raças. As alterações dos biomarcadores de estresses oxidativo pós-infecção variaram com a raça, tendo em comum ovinos Suffolk e Santa Inês um aumento de TOC no dia 28, seguido de um aumento de TAC no dia 42. Ovinos da raça Suffolk apresentaram maior carga parasitária em todos os momentos pós-infecção, sendo que nesta raça o OPG correlacionou-se com a concentração de oxidante total (TOC) (r=58; p<0,02) e na raça Santa Inês o OPG se correlacionou com a bilirrubina (r=0,49; p<0,02). As alterações dos marcadores de estresse oxidativo pós-infecção não foram associados à anemia e à hipoalbuminemia. Durante os primeiros 42 dias pós-infecção o... (Resumo completo, clicar acesso eletrônico Abaixo) / Abstract: There are some little evidence that tissue damage caused by gastrointestinal parasites in sheep promote oxidative stress, but the mechanisms that cause the imbalance between oxidants and antioxidants are not well established. This study aimed to prove the hypothesis that oxidative stress occurs in sheep infected with Haemonchus contortus and that this varies with racial resistance. Therefore, we investigated the relationship between oxidative stress caused by infection with H. contortus, the parasite load, anemia and hypoalbuminemia. To this end, Suffolk sheep breed (n = 15) and Santa Inês (n = 22) were wormed and after confirmed the absence of eggs in the feces (day 0), all animals were infected orally with 5000 third-stage larvae (L3) from H. contortus. The number of eggs per gram of feces (EPG) and the concentration of different plasma markers of oxidative stress (lipid peroxidation, albumin, uric acid, total bilirubin, total antioxidant capacity, total oxidant concentration and oxidative stress index) were quantified before (day 0) and 28, 32 and 42 days of experimental infection in both breeds. The amendments to the post-infection oxidative stress biomarkers varied with the race, having in common Suffolk and Santa Inês sheep the total oxidant concentration (TOC) increase on the 28th, followed by an increase of TAC on day 42. Breed Sheep Suffolk had higher parasite burden in all post-infection times, and this race the OPG correlated with the TOC (r = 58; p <0.02) and Santa Ines the OPG correlated with bilirubin (r = 0.49; p <0.02). The amendments to the post-infection oxidative stress markers were not associated with anemia and hypoalbuminemia. During the first 42 days post-infection with H. contortus, oxidative stress index varied according to race, in part due to increased oxidant production probably caused by tissue injury and also because of a probable compensatory ... (Complete abstract electronic access below) / Orientador: Paulo César Ciarlini / Banca: Carlos Noriyuki Kaneto / Banca: Raimundo Souza Lopes / Mestre

Current treatment methods for Acute Leukemia (AL) only provide temporary therapeutic efficacy as most patients will experience relapse within 2 years following first remission. Our lab has determined that vaccination with autologous cells infected with oncolytic virus MG1 can provide durable cures in a pre-clinical mouse model of AL. However, the mechanism(s) by which the infected cell vaccine (ICV) stimulates T cell dependent anti-tumour immunity and provides protection against tumour growth is unknown. This thesis was aimed to determine 1) what antigen presenting cell populations are activated post ICV immunization and 2) what T cell subsets are important in developing anti-tumour immunity during ICV immunization. My thesis has demonstrated that ICV immunization is more effective at inducing in vivo dendritic cell activation compared to irradiated L1210 cells alone and this activation may be a reason as to why we see improved anti-tumour efficacy in our ICV model. In addition, we have determined that CD4 T cells play an essential anti-leukemic role during ICV immunization and that neutralizing antibody production is a CD4 T cell dependent mechanism. Our data also demonstrates that both CD4 and CD8 T cell populations from ICV immunized mice provide a leukemia-specific anti-tumour immune response. Taken together, this data suggests that CD4 T cells may be acting as helper T cells to aid in the robust activation of leukemia-specific anti-tumour CD8 T cells. Our pre-clinical data characterizing the immune response has improved our understanding of the mechanism(s) which contribute to the efficacy of the ICV and will help provide a rationale framework with which to begin translating this treatment to clinical trials.

In this thesis, some issues about the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) have been addressed by concentrating on the stochastic modelling of the dynamics of the viruses. The aim of this thesis is to determine parameters such as the mean number of free HIV, infectious free HIV and non-infectious free HIV which are essential in determining incubation period of the virus, the disease progression of an infected individual and the efficacy of the treatment used. This thesis comprises of six chapters. The first two chapters are introductory to the viruses and reasons why HIV-1 is given priority over HIV-2 are given. The pathogenesis of the virus is addressed. This is because knowledge of the pathogenesis and strains of the virus has become essential in the study of HIV in vivo dynamics which is still paving ways into extensive research of the ways to contain the disease better. In chapter three the distribution functions of the HIV incubation period and seroconversion time are determined via stochastic models by building on previous work of Lui et al. (1988) and Medley et al. (1988). Also AIDS incidence projection was done using the Backcalculation method. Chapter four deals with the formulation of stochastic model of the dynamics of HIV in an infected individual. Two stochastic models are proposed and analysed for the dynamics of the viral load in a HIV infected person and the multiplication process of the virions inside an infected T4 cell. Also a numerical illustration of the stochastic models derived is given. In chapter five, the T4 cell count which is considered one of the markers of disease progression in HIV infected individual is examined. WHO has recently advocated that countries encourage HIV infected individuals to commence antiretroviral treatments once their T4 cell count is 350 cells per ml of blood. This is because when the T4 cell count is low, the T4 cells are unable to mount an effective immune response against antigens (and any such foreign matters in the body) and consequently, the individual becomes susceptible to opportunistic infections and lymphomas. We developed a stochastic catastrophe model to obtain the mean, variance and covariance of the uninfected, infected and lysed T4 cells; also the amount of toxin produced in a HIV infected person from the time of infection to the present time is derived. A numerical illustration of the correlation structure between uninfected and infected T4 cells, and infected and lysed T4 cells is portrayed. Antiretrioviral treatments were introduced while we await a cure. Treatment with single drug failed due to the fact that HIV evolved rapidly because of its high replication rate. Thus drug resistance to single therapeutic treatment in HIV infected individuals has promoted research into combined treatments. In chapter six a stochastic model under combined therapeutic treatment is derived. Mean numbers of free HIV, infectious free HIV and non-infectious free HIV are obtained. Variance and co-variance structures of our parameters were obtained unlike in previous work of Perelson et al. (1996), Tan and Xiang (1999). / Thesis (PhD)--University of Pretoria, 2009. / Statistics / unrestricted

Magister Chirurgiae Dentium (MChD) / Introduction: A common complication of poorly managed mandible fractures is infection. There is a consensus amongst clinicians in treating infected mandible fractures in an immediate setting. The approach includes drainage of the purulent discharge, debridement of the fracture, removal of teeth in the fracture line and immediate fixation. Fixation can be load bearing or load sharing in nature. Although clinicians advocate for the use of a reconstruction load bearing plate, a double miniplate fixation could be an alternative. Aim: The aim is to assess the outcomes of double miniplate osteosynthesis in the immediate management of infected mandible fractures Material and method: A prospective cohort study was conducted. The sample size was 20 (n =20). Infections were treated with an incision and drainage and the fractures fixated with a double miniplate fixation system. Pain scores, fracture union, fracture stability and surgical times were measured. Follow–up visits included one week, six weeks and three months respectively. Results: Mandibular angle fractures were most commonly infected. The most common cause of infection were teeth in the line of fracture. The buccal fascial space was the most commonly involved fascial space in regard to spread of infection. Nineteen of the twenty cases attained fracture stability. However, complications commonly encountered were persistent infection and wound dehiscence. Conclusion: Although a limited number of clinical cases were treated, the results correspond with the current literature when an immediate miniplate fixation protocol is used in infected mandible fractures. However, complications encountered in the study included the persistence of infection and wound dehiscence.

Introduction: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is subdivided according to the cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC) subtypes, each with different molecular profiles and clinical behaviour. This study aims to describe the pattern of the COO subtypes, the proportion of Epstein-Barr virus (EBV) co-infection, and their influence on survival outcomes in a setting of high HIV prevalence. Materials and Methods: This retrospective cohort study included patients diagnosed with de novo DLBCL NOS at our tertiary academic centre in Cape Town, South Africa over a 14-year period. Immunohistochemical stains were performed for COO classification, according to the Hans algorithm. Tumour EBV co-infection was established by EBV-encoded ribonucleic acid in situ hybridisation (EBER-ISH) staining. The effect of the COO subtypes and EBV co-infection on overall survival were described by means of univariate, bivariate and multivariate analyses. Results: A total of 181 patients with DLBCL NOS were included, which comprised 131 HIV-uninfected and 50 HIV-infected patients. There was an equal distribution of GCB and ABC subtypes in the HIV-infected and HIV-uninfected groups. EBV co-infection was detected in 16% of the HIV-infected cases and in 7% of the HIV-uninfected cases (p=0.09). There was no significant difference in the incidence of EBV co-infection between the GCB and ABC subtypes (p=0.67). HIV-infected patients with CD4≥150 cells/mm3 had similar survival to HIV-uninfected patients (p=0.005). Multivariate regression analysis showed that in the HIVinfected group with marked immunosuppression (CD4 <150 cells/mm3), there was significantly poorer overall survival compared to the HIV-uninfected group (HR 2.4, 95% CI 1.3–4.1). There were no statistically significant differences in overall survival by DLBCL COO subtype. Conclusions: There was no difference in the proportion of DLBCL COO subtypes, regardless of HIV status. EBV co-infection was more common in the HIV-infected group, but less than described in the literature. Unexpectedly, there were no significant differences in survival outcomes between the GCB and ABC subtypes. Higher CD4 counts in the HIV-infected group had good survival outcomes, while lower CD4 counts predicted adverse survival outcomes. Further research is needed to explore the genetic mutational landscape of HIVassociated DLBCL.

ABSTRACT Regulatory T cells (Tregs) are CD4+ T lymphocytes that express the gene FOXP3 and suppress other cellular immune responses. Their role in HIV pathogenesis is uncertain. Regulatory T cell (Treg) levels were analysed in peripheral blood of HIV infected patients and controls in South Africa. Immunophenotypic analysis revealed significantly elevated levels of FOXP3 positive Tregs in HIV infected patients (median 6.8%) compared with controls (median 3.7%). Treg levels were inversely correlated with CD4+ T cell count. FOXP3 mRNA expression was dependent on choice of reference gene (GAPDH or 18sRNA) and did not correlate with FOXP3 protein expression analysed flow cytometrically. These findings illustrate that Tregs are elevated in the peripheral blood of patients with late stage HIV disease and suggest a role for Tregs in the clinical immune suppression seen in these patients. Tregs may prove to be useful therapeutic targets for intervention or as a prognostic monitoring tool.

Background: Breastfeeding amongst HIV-infected and HIV-exposed mother-infant dyads is a wide-ranging and persistent field in which more investigation is needed. The literature widely recognizes the multifactorial and syndemic nature of HIV and infant feeding, specifically pertaining to maternal and other breastfeeding-associated risks. Findings differed regarding breastfeeding and general developmental outcomes amongst HIV-exposed and HIV-infected infants when compared with HIV-unexposed infants. Evidence, however, suggests slight neurodevelopmental differences in HIV-exposed infants when compared with HIV-unexposed infants, suggesting possible feeding differences. Recent literature also indicated a lack of knowledge among allied health care staff regarding evidence-based counselling content to be provided to mothers concerning single option feeding, breastfeeding outcomes and risks in HIV-affected mother-infant dyads in South Africa. Owing to these varied findings related to HIV-affected mother-infant dyads, synthesising of knowledge regarding HIV, infant breastfeeding outcomes and associated risk factors is warranted. Objective: To critically appraise recent literature regarding breastfeeding outcomes and associated risks in HIV-infected and HIV-exposed infants using the PRISMA-P statement guidelines. Method: Five electronic databases were systematically searched to obtain English publications from the last ten years pertaining to breastfeeding outcomes and associated risks of HIV-infected and HIV-exposed infants and children. Grey literature sources were also included. Data were extracted according to various data items and were synthesised using thematic synthesis. Results: Of the initial 7151 sources identified, 42 articles were deemed eligible for final inclusion. The final selection included 19 cohort studies and two expert committee reports, classified as grey literature. The remaining 21 studies compromised of case-control, cross-sectional, and randomized controlled trial studies. The following themes were identified from the review objectives: breastfeeding outcomes, breastfeeding risk factors, infant growth and developmental outcomes and barriers and facilitators to feeding decisions. Most studies focused on HIV-exposed infants’ growth and developmental outcomes. Exclusive breastfeeding was confirmed to have the best outcomes for all infants, regardless of their HIV status, which in turn supports national and international policies. The most prevalent factors that made it difficult for mothers to breastfeeding were maternal factors affecting decision-making for breastfeeding, followed by biological risk factors. Conclusion: Knowledge regarding breastfeeding outcomes in HIV-exposed and HIV-infected infants remains lacking and further research is necessary. This review emphasised that the majority of HIV-affected mother-infant dyads reside in sub-Saharan Africa, illustrating that health professionals, especially those in sub-Saharan Africa (SSA), have to look beyond their traditional assessment and management focuses to include the factors that can impact successful exclusive breastfeeding. Addressing both infants’ needs and maternal HIV-related needs and risks on macro, meso, and microsystem levels is necessary. / Dissertation (MA (Speech-Language Pathology))--University of Pretoria, 2021. / Speech-Language Pathology and Audiology / MA (Speech-Language Pathology) / Unrestricted

Bakgrund: Hiv är ett folkhälsoproblem som cirka 30-35 miljoner människor runt om i världen lever med. I Sverige rapporteras 400-500 nya fall varje år. Att ha hiv kan leda till att människor utsätts för stigmatisering från omgivningen. Syfte: Syftet med denna litteraturöversikt är att belysa upplevelser av stigmatisering hos människor som har hiv. Metod: En litteraturöversikt genomfördes där tio vetenskapliga artiklar valdes med både kvalitativa och kvantitativa studier. Resultat: Resultatet presenterades i fyra huvudteman: Upplevelsen av social stigmatisering, Självstigmatisering hos människor som lever med hiv, Fysiskt avstånd och Att uppleva psykisk ohälsa. Diskussion: Resultatet har diskuterats utifrån omvårdnadsteoretikern Katie Eriksson om den caritativa vårdteorin samt fyra konsensusbegrepp som hon har beskrivit: den mångdimensionella hälsan, lidande- en del av hälsan, vårdande- att lindra patientens lidande och den unika människan. Resultatet har även diskuterats genom Erikssons tolkning av: försoning och värdighet. / Background: HIV is a public health problem that about 30-35 million people live with around the world. HIV. 400-500 new cases are reported each year in Sweden. Having HIV can lead to stigmatization from people around you. Aim: The experience of stigmatization in people who are living with HIV. Method: The literature review was based on ten scientific articles, both qualitative and quantitative studies. Results:  The results were presented in four main themes: Experiences of social stigmatization, Self-stigmatization with people who are living with HIV, Physical distance and Experiences of mental illness. Discussion: The result has been discussed based on nursing theorist Katie Eriksson´s theory about the caritative theory and the four consensus concepts she mentioned: the multi-dimensional health, suffering- a part of health, care- to relieve the patient´s suffering and the unique human. The result has also been discussed through Eriksson´s important concepts such as: atonement and dignity.

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Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus, often acquired during childhood, that currently infects more than 50% of the human population. The symptoms of infection are herpetic lesions that frequently appear throughout a host's life in response to stress in the orofacial or genital region. As a pathogen, HSV-1 replicates rapidly in epithelial cells, but it is also capable of infecting neurons where it can pursue a lytic or latent infection. Latency is a state of viral quiescence where the virus can persist indefinitely yet remain poised to reactivate. Latency is unique to herpesviruses and key to HSV's success, but the molecular mechanisms that govern this state are unclear. A virus-encoded E3-ubiquitin ligase, Infected Cell protein 0 (ICP0), is often correlated with latency establishment but is detected in opposition to the state of latency. During lytic infection, ICP0 has many biological roles but primarily catalyzes the addition of ubiquitin to target substrate, marking proteins for degradation or altering their function. This ubiquitination ability allows ICP0 to alter the intracellular environment making neurons conducive to lytic or latent HSV-1 infection. ICP0's neuron-specific targets, however, are unknown, representing a significant gap in knowledge. Through the studies presented in this dissertation, we identified some of the neuron-specific ubiquitination targets of ICP0 in neurons. We utilized primary adult sensory neurons of the dorsal root ganglia and HSV-1 viral strains KOS, wild-type virus encoding a fully functional ICP0, and HSV-1 n212, encoding a truncated ICP0 protein, to illuminate the mechanisms involved in establishing and maintaining HSV latency. By using adult primary neurons and functional HSV-1 strains with and without ICP0, we were able to show that ICP0 regulates host and viral proteins during the initial onset of neuronal infection. We also show that based on neuronal conditions set forth before HSV-1 initial infection, host proteins will influence HSV-1 viral proteins to repress viral gene expression, thereby promoting the establishment of latency. / Doctor of Philosophy / Herpes simplex virus (HSV-1) is a virus, often acquired during childhood, that more than 50% of people have. Those who are infected with HSV-1 often have cold sores that appear in response to stress on the face or on the genitals. As a virus, HSV-1 replicates around the eyes, nose, and mouth but can also infect neurons where it can continue to replicate or establish latency. Latency is when the virus is inside the neurons but is unnoticeable and can reappear in response to stress. The state of latency is unique to herpesviruses and key to the success of HSV-1, but scientists are unsure of how it works. A protein made by the virus, Infected Cell Protein 0 (ICP0), is often correlated with the state of latency but is often present when the virus is not latent. ICP0 does a lot to support HSV-1, but it primarily destroys proteins that prevent the virus from replicating. By destroying proteins that prevent HSV-1 replication, ICP0 can help the virus make more viruses. The proteins that are destroyed by ICP0 are currently unknown, which represents a significant gap in knowledge. Through the research conducted in this dissertation, we identified some of the proteins that ICP0 destroys in neurons. We utilized neurons from the dorsal root ganglia and HSV-1 viral strain KOS, which encoded a functional ICP0, and n212, which encodes a nonfunctional ICP0, to study the mechanisms used by the virus to infect neurons. By using HSV-1 viruses with and without ICP0, we were able to show what proteins ICP0 destroys during infection in neurons. We were also able to show that HSV-1's ability to establish latency is dependent on how the neurons handle the initial onset of infection. Overall, a combination of host and viral proteins coordinates the virus's ability to establish latency and persist within a host.