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Background: Burnout and physician wellness are becoming increasingly topical. While some surveys have been performed with South African anaesthesiologists, these have been conducted in limited samples. While Burnout is often measured, there is a paucity of research on contributory risk and protective factors. Method: A contextual, prospective, cross-sectional study was conducted. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) and the Areas of Work-Life Survey (AWS) were used to assess Burnout and contributory organizational risk factors amongst state-employed anaesthesiologists working at Groote Schuur Hospital. Results: Out of a possible 127 members of staff (Medical officers, Registrars and Consultants), 81 responded with 75 completing the full survey (59% response rate). Only 4% of respondents were classified as “burnt out”, defined as scoring 8 high in all three domains of Burnout: High Emotional Exhaustion and Depersonalization and Low Personal Accomplishment. However, 67% of respondents scored high for at least one of the components of Burnout, indicating the majority of the respondents are at risk for developing clinically significant Burnout. The Areas of Work-Life survey showed that respondents found their workload inappropriate. However, responses for the categories of Control, Reward, Community, Fairness and Values were all in the acceptable range. Conclusion: While the overall rate of Burnout was low, the majority of respondents were at risk of developing Burnout. High perceived workload appeared to be a particular contributory factor. Protection against Burnout in this group may be provided by a combination of few organisational risk factors together with feelings of personal accomplishment.

Burnout due to work-related stress is increasing in the society. Many studies concern the causes and effects of burnout, but rarely concern the experiences of those who are living with burnout. The aim of this study was to examine the experience of living with burnout. The concepts of health, suffering, burnout, stress and coping are briefly described in the background. The method that was used is a literature-based study with the analysis of qualitative research. This study is based on eight qualitative articles. Six themes emerged; Physical experiences, Psychological experiences and Existential experiences, Work experiences, Experiences of relations in private life and Experiences of demands and expectations. The results shows that burnout affects a person on many different levels. Dealing with burnout involves a range of varieties of symtoms, physical as well as psychological and social. Physical symtoms that appeared among the participants were for instance fatigue, brain fog, headache and palpitations. Social and relational problems as bad conscience, low self- esteem and feelings of inadequacy were experienced. Emotional disturbances and existential reflections were common amongst those who were suffering from burnout.

Burnout is a condition that results from chronic work-related stress, and it is associated with impairments in cognitive and emotion-related functions, such as impaired executive functions and emotion regulation. This thesis aimed to conduct a systematic review of the neural correlates of burnout. The thesis investigates the following research question: do the neural correlates of burnout involve the same brain regions and/or functions as those implicated in the cognitive functions affected by burnout? The systematic literature search resulted in seven studies which studied either the functional, structural, or electrophysiological correlates of burnout. The results showed that burnout involves functional and structural alterations in regions involved in various higher-order cognitive functions. Structural findings indicate alterations in brain regions involved with emotion processing, memory and attention (i.e., medial prefrontal cortex, caudate, amygdala). Electrophysiological findings indicate differences in alpha power in burnout individuals compared to controls, suggesting that alpha power is reduced when burnout's specific symptoms (i.e., exhaustion) increase. Evident are also findings on functional differences in working memory (dorsolateral prefrontal cortex) and reduced functional connectivity between emotion processing areas (the amygdala and anterior cingulate cortex) and areas such as the motor cortex. The presented findings answer the research question. It can be concluded that the brain regions implicated in the cognitive functions affected by burnout resemble many of the regions affected in the neural correlates of burnout. Future studies should take into account the methodological issues of the existing studies.

Monocytes are dynamic innate immune cells that respond differently based upon the dose and duration of an infection. While super low dose endotoxin is found in chronic inflammatory diseases such as atherosclerosis, exposure to high dose endotoxin leads to sepsis. However, clear characterization of monocytes and the underlying mechanisms in these disease conditions is lacking. To elucidate the missing information, we conducted two different projects. In the first project, we investigated the role of super low dose endotoxin in polarizing monocytes to a prolonged low-grade inflammatory state with no resolution, disrupting homeostasis. This low grade inflammatory phenotype was confirmed by sustained induction of inflammatory mediators CD40 and CD11a. In addition, low grade inflammatory monocytes influence neighboring T cells by suppressing T cell regulatory functions. Mechanistically, we showed that the non-resolving inflammatory phenotypes in monocytes is dependent on non-traditional TLR4 adaptor called TRAM. In the second project, we focused on the effects of high dose endotoxin on monocyte phenotypes. We reported that high dose endotoxin give rise to a mix of both immunosuppressive and pathogenic inflammatory monocytes, leading to monocyte exhaustion. While thorough research is conducted to study the immunosuppressive monocytes and underlying long term effects, role of pathogenic inflammatory monocytes is not well addressed. Monocyte exhaustion leads to elevated levels of CD38, an inflammatory mediator, elevated ROS levels, depleted NAD+ and mitochondrial respiration. STAT1 and KLF4 are critical transcription factors in sustaining exhausted phenotypes. Indeed, TRAM adaptor molecule also mediates this exhaustion as TRAM deletion restores monocyte health. Taken together, our work defines novel monocyte phenotypes and mechanism in super-low dose or high dose endotoxin environments. / Doctor of Philosophy / Healthy inflammatory response is represented by initial induction of inflammatory cells in the site of infection and pathogen clearance, followed by resolution of inflammation and damage repair. This balance between inflammation and resolution maintains immune homeostasis. Imbalances in this homeostasis can be a cause or effect of various disease conditions such as atherosclerosis and sepsis, for example. Despite rigorous research, these diseases are still prevalent and treatments are still lacking. It is essential to investigate inflammatory responses at a cellular level and understand how an immune cell responds to a given pathogen. Depending upon the intensity, dose and duration of a pathogen can dictate immune cell functions. Recent discoveries, including the research in our lab have reported that super low dose bacterial endotoxin exacerbates atherosclerosis. Mouse monocytes (innate immune cells) treated with super low dose endotoxin continuously induce mild but sustained inflammatory molecules but are unable to exhibit resolving mediators to dampen the inflammation and hence, monocyte homeostasis is disrupted. Homeostatic imbalance is also in seen in sepsis, when monocytes exposed to high dose bacterial endotoxin. Due to a repetitive exposure to high dose endotoxin, monocytes are unable to respond accurately, where they simultaneously exhibit inflammatory and anti-inflammatory mediators but in a dysregulated manner.

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Master of Science / Animal Sciences and Industry / John M. Gonzalez / Pigs fed ractopamine-HCl (RAC) are more prone to fatigue and exhaustion when improperly handled. Wireless electromyography (EMG) can be used to directly measure median power frequency (MdPF) and root mean square (RMS) as indicators of action potential conduction velocity and muscle fiber recruitment, respectively. The objectives of this study were to determine the effect of RAC on exhaustion, EMG measures, and muscle fiber type characteristics when barrows were subjected to increased levels of activity. Thirty-four barrows were assigned to one of two treatments: a commercial finishing diet containing 0 mg/kg (CON) RAC or a diet formulated to meet the requirements of finishing barrows fed 10 mg/kg RAC (RAC+) for 35 d. After 32 d of feeding, barrows were walked around a circular track at 0.79 m/s until subjective exhausted was reached. Time, distance, and speed were measured. Wireless surface EMG sensors were affixed to the Deltoideus (DT), Triceps brachii lateral head (TLH), Tensor fasciae latae (TFL), and Semitendinosus (ST) muscles. After harvest, samples of each muscle were collected for fiber type, succinate dehydrogenase, and capillary density analysis. Speed was not different (P = 0.82) between treatments, but RAC+ barrows reached subjective exhaustion quicker and covered less distance than CON barrows (P < 0.01). The end-point MdPF was not affected by the RAC diet. The RAC diet did not change end-point RMS values in the DT or TLH; however, the RAC+ barrows tended to have decreased ST and increased TFL end-point RMS values (P < 0.07). The percentage of type I fibers tended to be greater (P = 0.07) in RAC+ barrows, but the RAC diet tended to increase (P = 0.07) size of type I fibers and increase (P = 0.03) the size of type IIA fibers. Succinate dehydrogenase was not different between treatments. The RAC+ barrows had more (P = 0.03) capillaries per fiber than CON barrows. A diet containing RAC contributes to increased onset of subjective exhaustion, possibly due to rapid loss of active muscle fibers and chronic loss of oxidative muscle fibers with no change in muscle metabolism.

A balanced immune response is required to mediate clearance of a virus infection without immune-mediated disease. CD4 and CD8 T cells are capable of both exerting antiviral effector functions and regulating the immune response. The regulatory T cell (Treg) subset of CD4 T cells helps to modulate immune activation and inflammation. During respiratory syncytial virus (RSV) infection in mice, conventional CD4 T-cell-mediated cytokine production has been shown to contribute to immune-mediated pathology. I demonstrate that Tregs are critical to control immunopathology during RSV infection. This was demonstrated through diphtheria toxin (DT)-mediated Treg elimination in a mouse strain expressing the DT receptor (DTR) under the control of the Foxp3 promoter. However, these mice were unable to maintain extended Treg depletion limiting the effectiveness of this model. In addition, DT-treated wild-type (WT) mice were found to be a necessary control for adverse DT-induced disease. In humans, I have shown that activated Tregs are reduced in the peripheral blood of RSV-infected infants compared to controls. RSV-infected infants also exhibited an increased proinflammatory cytokine response in nasal aspirates. However, the alarmin cytokine IL-33, which has been shown to mediate Treg homeostasis, was the only cytokine that exhibited reduced protein levels in RSV-infected infants compared to controls. Thus, severe RSV infection in infants may be due to lack of proper Treg-mediated immune regulation. Similar to RSV, regulation of the T cell response during chronic viral infection with lymphocytic choriomeningitis virus (LCMV) is vital to prevent immune-mediated pathology. During LCMV and human chronic viral infections, CD4 and CD8 T cells exhibit T cell exhaustion where they lose the ability to exert effector functions. However, a functional CD4 and CD8 T cell response is required for viral clearance. During human chronic viral infection, an association between increased CD4 and CD8 T cell function and enhanced viral control has been identified that can be influenced by genetic factors. I aimed to identify the contribution of the host genetic factors that contribute to enhanced CD8 T cell function and viral control using the LCMV model. I found that increasing the major histocompatibility complex (MHC) diversity resulted in enhanced viral control in both a C57BL and BALB genetic background. Thus, induction of a broader T cell response was associated with enhanced viral control. However, mice expressing a heterozygous MHC on the C57BL background also exhibited mortality following chronic viral infection. Both CD4 and CD8 T cells were shown to contribute to this mortality and exhibited reduced T cell exhaustion during LCMV infection in these mice. Heterozygous MHC expression on the C57BL mouse background was also associated with an increased T helper (Th)-1 skewed CD4 T cell response compared to mice on the BALB background. Furthermore, CD4 T-cell-mediated IFN-γ production contributed to both CD8 T cell effector activity and mortality during chronic LCMV infection. Thus, both T cell epitope diversity and host genetics contribute to LCMV-induced mortality. Collectively, my data highlight both the need for effective immune-meditated viral control and regulation of T-cell-mediated pathology during both acute and chronic viral infections.

Burnout is a topic that is drawing an increasing amount of attention in the social work field. The compassion and emotional energy that is used daily by these service providers can cause them to experience emotional exhaustion, depersonalization, and reduced personal accomplishment. The effects of burnout are detrimental on several levels. Staff will experience decreased interest and efficiency in their work and may even leave their place of employment. Clients will not receive the help that they require and agencies will suffer from staff turnover and lowered productivity. Utilizing a survey including a burnout inventory and spirituality inventory, data was gathered regarding burnout and the spiritual attitudes and practices of 133 service providers. Results show that there is a negative significant relationship between depersonalization and spirituality. There was a positive significant relationship between personal accomplishment and spirituality. The correlation showed that personal accomplishment was negatively related to emotional exhaustion as well as depersonalization. These results are consistent with the literature in the way that it demonstrates that the use of spiritual beliefs and practices can reduce the effects of burnout on social workers.

Bakgrund: Långtidssjukskrivning på grund av stressrelaterad ohälsa har under senaste åren ökat i Sverige. Det medför oftast ett stort lidande för den enskilde och ger även ökade kostnader för samhället. Hur rehabiliteringen genomförs är av vikt för att kunna hjälpa personerna som är långtidssjukskrivna tillbaka till familjeliv och arbetsliv. Därför är det viktigt att få ta del av de sjukskrivnas egna erfarenheter av rehabiliteringen. Syftet: Var att undersöka hur personer som är långtidssjukskrivna &gt; 3 månader på grund av långvarig stress har upplevt sin rehabilitering och vad som har underlättat för återgång till familjeliv och arbetsliv. Metod: Semistrukturerade intervjuer med 4 kvinnor och 1 man (n= 5) har genomförts. Kvalitativ innehållsanalys har använts vid analys av data. Resultat: Följande fem kategorier framkom: Förändringar i arbetslivet, förändringar i det dagliga livet, försäkringskassans, arbetsförmedlingens och arbetsgivarens betydelse, framgångsfaktorer i rehabiliteringen och strategier för att hantera stress. Slutsats: Denna studie visar på betydelsen av att lyssna på personen som är sjukskriven för att kunna upprätta en individuell rehabiliteringsplan. Att ha ett holistiskt perspektiv, för att kunna se helheten och att alla rehabiliteringsaktörer jobbar mot samma mål är viktigt. / Background: Long-term sickness absence due to stress-related illness has increased during recent years in Sweden. Most often the sick-leave entails a great suffering for the individual, as well as increased costs for society. How the rehabilitation is carried out is of importance to help people who are on sick-leave to return to work and family life. Therefore it is importance to listen to these peoples own experience of the rehabilitation. Aim: To examine how people on sick leave &gt; 3 months because of prolonged stress have experience their rehabilitation and what has facilitated for the return to family and work. Method: Semi-structured interviews were conducted with 4 women and 1 man (n= 5) Data was analyzed by qualitative contens analysis. Results: The following five categories were identified: Changes in work life, changes in daily life, insurance offices, empolyment office and employer’s role, successful factors in the rehabilitation and strategies to cope with stress. Conclusion: This study demonstrates the importance of listening to the person who is on sick leave in order to prepare an individual rehabilitation plan. To have a holistic perspective in order to see the big picture and that all rehabilitation actors are working towards the same goal is important.