The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs.

Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared with the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.

Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared with the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.

This study develops and tests a model which investigates the simultaneous effects of job demands, job resources, and a personal resource (intrinsic motivation) on emotional exhaustion and turnover intentions. Frontline hotel employees in Ankara, Turkey serve as the study setting. Among others, results show that job demands (role conflict and role ambiguity) trigger frontline employees' emotional exhaustion and turnover intentions. Job resources (supervisory support, training, empowerment, and rewards) and intrinsic motivation reduce emotional exhaustion. Implications of the findings are discussed and directions for future research are offered.

Background microRNA-23b (miR-23b) is a multiple functional miRNA. We hypothesize that miR-23b plays a role in the pathogenesis of sepsis. Our study investigated the effect of miR-23b on sepsis-induced immunosuppression. Methods Mice were treated with miR-23b inhibitors by tail vein injection 2 days after cecal ligation puncture (CLP)-induced sepsis. Apoptosis in spleens and apoptotic signals were investigated, and survival was monitored. T-cell immunoreactivities were examined during late sepsis. Nuclear factor B (NF-B)-inducing kinase (NIK), tumor necrosis factor (TNF)-receptor associated factor 1 (TRAF1), and X-linked inhibitor of apoptosis protein (XIAP), the putative targets of miR-23b, were identified by a dual-luciferase reporter assay. Results miR-23b expression is upregulated and sustained during sepsis. The activation of the TLR4/TLR9/p38 MAPK/STAT3 signal pathway contributes to the production of miR-23b in CLP-induced sepsis. miR-23b inhibitor decreased the number of spleen cells positive by terminal deoxynucleotidyl transferase dUTP nick-end labeling and improved survival. miR-23b inhibitor restored the immunoreactivity by alleviating the development of T-cell exhaustion and producing smaller amounts of immunosuppressive interleukin 10 and interleukin 4 during late sepsis. We demonstrated that miR-23b mediated immunosuppression during late sepsis by inhibiting the noncanonical NF-B signal and promoting the proapoptotic signal pathway by targeting NIK, TRAF1, and XIAP. Conclusions Inhibition of miR-23b reduces late-sepsis-induced immunosuppression and improves survival. miR-23b might be a target for immunosuppression.

El objetivo de la presente investigación es encontrar la relación entre las variables del síndrome de burnout y estilos de afrontamiento de los Oficiales de la Marina de Guerra del Perú. El tipo de investigación es de diseño descriptivo correlacional y de corte trasversal no experimental, la muestra estuvo constituida por 336 Oficiales de Marina de Guerra, cuyas edades fluctúan entre los 21 y 53 años. Se utilizó como instrumentos el inventario de Síndrome de burnout y el Cuestionario de Estilos de Afrontamiento al estrés. Los resultados indican que existe relación significativa entre el Síndrome de Burnout y los de Estilos de Afrontamiento al estrés en Oficiales de la Marina de Guerra del Perú. A nivel específico, existe relación significativa entre la dimensión agotamiento emocional y las dimensiones de los estilos de afrontamiento al estrés. Existe relación significativa entre la dimensión de despersonalización y las dimensiones de los estilos de afrontamiento al estrés. Por último, existe relación significativa entre la dimensión de realización personal y las dimensiones de los estilos de afrontamiento al estrés. / The type of research is of a descriptive correlational design and non-experimental cross-sectional design, the sample consisted of 336 Navy Officers, whose ages fluctuate between 21 and 53 years. The Burnout Syndrome inventory and the Coping Styles Questionnaire were used as instruments. The results indicate that there is a significant relationship between the Burnout Syndrome and the Coping Styles in Officers of the Peruvian Navy. At a specific level, there is a significant relationship between the emotional exhaustion dimension and the dimensions of coping styles. There is a significant relationship between the depersonalization dimension and the dimensions of coping styles. Finally, there is a significant relationship between the dimension of personal fulfillment and the dimensions of coping styles. / Trabajo de investigación

In 2014 Bodenheimer and Sinsky published the Quadruple Aim model, which argued that healthcare provider wellbeing was the missing link to improving patient and population health outcomes, as well as cost containment. Rather than treating burnout, however, experts in fields outside healthcare are finding validity in promoting thriving at work as a means to prevent burnout and improve employee satisfaction, engagement, and productivity. The purposes of this study were to investigate the relationship between thriving and emotional exhaustion (which is widely considered a core element of burnout) in healthcare providers, and the impact thriving had on primary care population health outcomes as measured by quantifiable value-based quality performance metrics. Using Georges' (2013) Emancipatory Theory of Compassion and Bodenheimer and Sinsky's Quadruple Aim as conceptual frameworks, this descriptive, non-experimental study used advanced applied biostatistical techniques to analyze archival data from the December 2018 UCHealth Physician and Advanced Practice Provider Voice Survey as well as provider performance scores from the same time period. Results of the study were mixed, showing that while there is an inverse relationship between thriving and emotional exhaustion in healthcare providers, thriving did not predict population health outcomes. By evaluating thriving in healthcare providers in relation to emotional exhaustion and in context of value-based health care delivery systems, this study was the first of its kind. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

On the 19th of December 2019, the Court of Justice of the European Union ruled: "The supply to the public by downloading, for permanent use, of an e-book is covered by the concept of ‘communication to the public’ ..." This judgment ("Tom Kabinet judgment") solved a long debate whether "digital exhaustion" exists or not, in favour of the latter. This study is dedicated to the analysis of Tom Kabinet judgment and its effects. It analyses the judgment from several perspectives. Firstly it discusses the effects and the importance of Tom Kabinet judgment. Secondly, it analyzes the legal and non-legal arguments of the Court from a critical point of view and argues that a contrary non-contra legem solution existed. Thirdly, this study argues that in the long run, not only the end-users but also the rightholders can benefit from "digital exhaustion" and the existence of a digital secondary market. Therefore, a contrary solution of the case could be beneficial for everyone. As a proponent of "digital exhaustion," the present author offers several legislative policy considerations that are needed to give a new life to digital secondary markets.

Purpose: Leadership is one of the very important as well as decisive factors in business environment. Following the Blau’s social exchange theory, this study discussed to analyze the despotic leadership effect on employees' job satisfaction in the Pakistani context. This research also analyzes the indirect association of despotic leadership and job satisfaction through the third variable named, emotional exhaustion (as mediator).  Method: Data is collected through an online self-administrated survey from employees working in the hotel industry of Pakistan. Descriptive analysis and inferential statistics were used. Moreover, conditional process technique was used introduced by Preacher and Hayes. Results: In conclusion, this study illustrates that despotic leadership style of the employees in hotel industry is a main antecedent of poor job satisfaction of the employees and this low job satisfaction becomes More low when employee experience the feelings of emotional exhaustion. Importantly, in this study it is found that emotional exhaustion does not mediate the relationship between despotic leadership and job satisfaction.  Originality: This research had added value to the existing literature on negative supervision in the hospitality sector, specifically in Pakistan. This has suggested organizations to identify prevalent despotic leaders and establish accountability mechanisms within the organizations.

Syftet med den föreliggande studien var att undersöka huruvida arbetsrelaterade krav och arbetsrelaterade resurser kunde predicera utmattning hos förskolepersonal (N = 114). Studien genomfördes med en korrelationell design där de validerade enkäterna COPSOQ III och KUS-26 användes för att samla in data. Analysen genomfördes med tre hierarkiska multipla regressionsanalyser som visade att arbetsrelaterade krav och arbetsrelaterade resurser tillsammans kunde predicera utmattning. Arbetsrelaterade krav kunde predicera utmattning med ett positivt samband, medan arbetsrelaterade resurser inte på egen hand kunde predicera utmattning när de förekom i samma modell som arbetsrelaterade krav. Känslomässiga krav och kvantitativa krav var de typer av arbetsrelaterade krav som positivt kunde predicera utmattning. Socialt stöd från överordnad var den enda typen av resurs som kunde predicera utmattning med ett negativt samband. Sammanfattningsvis visade den föreliggande studien att arbetsrelaterade krav tycks vara en större riskfaktor än bristande arbetsrelaterade resurser när det kommer till utmattningsproblematik hos svensk förskolepersonal. / The aim of this study was to investigate whether job-demands and resources could predict exhaustion in Swedish preschool personnel (N = 114). The study was done using a quantitative method where the validated questionnaires COPSOQ III and KUS-26 were used to gather the data. Using 3 hierarchical multiple regression analyzes the present study showed that job-demands and resources could predict exhaustion. Job demands could positively predict exhaustion. However, job resources could not on its own predict exhaustion when occurring in the same model as job demands. The present study showed that emotional and quantitative demands were the types of demands that could positively predict exhaustion. Social support from supervisor was the only type of resource that could negatively predict exhaustion. In conclusion, the study showed that for Swedish preschool personnel, high job demands are a greater risk factors for exhaustion than lacking job resources.