Little research has been done on the personality of internal auditors. However, there does exist a negative stereotype. They are seen as hostile and unsympathetic. The purpose of this research was to see if the negative stereotype was indeed true and to see if undesirable behavior could be changed through training.

The Class Pass Intervention (CPI) is designed for students who engage in escape-motivated problem behavior to avoid or escape difficult or aversive academic work and who are not responsive to the system-wide universal supports provided to all students. Research on the CPI is in its initial stages and requires replications to be proven effective in multiple settings and become evidenced-based. Therefore, the purpose of the study was to expand the literature on CPI by targeting elementary school students and assess its impact on decreasing disruptive behavior maintained by attention and on increasing academic engagement. The study involved 4 students with disruptive classroom behavior and low academic engagement and their 2 classroom teachers. A multiple-baseline design across participants was used to demonstrate the intervention outcomes. The intervention was implemented during a targeted routine or academic time period when behavior was most likely to occur. Results indicated that teachers implemented the CPI with high levels of fidelity, and their implementation was effective in increasing academic engagement and decreasing disruptive behavior with all participants. The intervention effects were maintained after undergoing fading for all 4 students and during 2-week follow-up for 2 students. The results of social validity assessments indicated students and teachers found the intervention to be acceptable and effective. Limitations and implications for future research are discussed.

Although numerous studies have shown that discrimination contributes to poorer mental health, the precise mechanisms underlying this association are not well understood. In this paper, we consider the possibility that the association between day-to-day discrimination (being disrespected, insulted, and harassed) and depressive symptoms is partially mediated by religious struggles (religious doubts and negative religious coping). To test our mediation model, we use data collected from the 2011 Miami-Dade Health Survey (n = 444) to estimate a series of multiple regression models assessing associations among day-to-day discrimination, religious struggles, and depressive symptoms. We find that day-to-day discrimination is positively associated with religious struggles and depressive symptoms, net of adjustments for general religious involvement, age, gender, race, ethnicity, immigrant status, interview language, education, employment, household income, financial strain, and marital status. We also observe that religious struggles are positively associated with depressive symptoms. Our mediation analyses confirm that day-to-day discrimination can contribute to depressive symptoms by stirring religious struggles. Our key finding is that religious struggles may serve as a maladaptive coping response to discrimination. Our analyses extend previous work by bridging research in the areas of discrimination, religious struggles, and mental health.

Introduction: Older persons represent a quickly growing segment of the population worldwide and more vulnerable population to various adverse drug reactions and adverse outcomes. Many explicit criteria of potentially inappropriate medications (PIMs) have been developed in different countries in order to improve the quality and safety of geriatric prescribing and to reduce the risk of drugs in older adults. The aim of this diploma thesis was to summarize (using narrative literature review) the negative outcomes of potentially inappropriate medications documented in pharmacoepidemological studies published by 2016 year. The outputs of diploma thesis create a part of the effort of the research subgroup "Aging and Changes in the Therapeutic Value of Medications in the Aged" and EU COST Action initiative IS1402 (2015-2018). Methods: The literature review using PubMed and Web of Science datasets during the period 10/2015 - 1/2017 was conducted. 421 studies were identified during the primary literature search and after thorough consideration of abstracts 67 (16%) of studies were selected for works on summary tables (354 of studies were excluded because in these studies only prevalence of PIMs, no negative outcomes were documented, or PIMs were defined based on implicit criteria or full text of articles...

Cancer, a global epidemic, is a major cause of morbidity and mortality affecting populations in all nations and regions. Breast cancer (BC) is the second most common cancer in the world and the most fatal malignancy affecting women both in the developed and developing countries. Even with the improvement in overall survival of BC patients due to early detection and advancement with systematic therapy, triple negative breast cancer (TNBC), an aggressive subtype of BC still remains a major challenge as it lacks targetable receptors. Chemotherapy is the main treatment for TNBC. However, de novo and acquired resistance to conventional anticancer drugs is a major limitation and cause of therapeutic failure. Cancer stem cells (CSCs) are believed to be responsible for chemoresistance and tumour relapse. My study demonstrates that hypoxia is involved in the development and maintenance of these CSCs traits in TNBC, as cells grown in hypoxia are significantly resistant to several first line anti-BC drugs. Hypoxia-induced activation of nuclear factor kappa B (NFB) and hypoxia inducible factors (HIFs) also play pivotal roles in chemoresistance. Forced expression of NFB and HIFs by transfection with p65 subunits of NFB and HIF1α and 2α subunits induced CSCs characters and resistance to a range of anticancer drugs in TNBC cell lines. My study also indicated a positive loop between the activation of NFB and HIFs. Therefore development of novel medicine to interfere the pathways of hypoxia and NFB may efficaciously target CSCs and reverse chemoresistance which will be of clinical significance for TNBC treatment. iv Disulfiram (DS) is a commercially available anti-alcoholism drug. Recent studies demonstrate that it is highly cytotoxic in a wide range of cancer types and potentially repurposed as an anticancer drug. The anticancer mechanisms of DS were investigated in this study. The results from my study indicate that the cytotoxicity of DS is copper (Cu) dependent with a biphasic manner. The instant cytotoxic phase is induced by the extracellular reactive oxygen species (ROS) generated by the reaction between DS and Cu. The delayed killing is caused by the complex diethyldithiocarbamate (DDC) and Cu (DDC-Cu), the final product of the reaction. The cytotoxicity of both phases needs the intact DS. However, due to the extremely short half-life of DS in the bloodstream, the anticancer efficacy of DS has been severely hampered in vivo and in patients. Nanotechnology-based drug delivery system is a rapidly evolving and expanding interdisciplinary field involving in an amalgamation of chemistry, engineering, biology and medicine. In the last part of my study, I have successfully encapsulated DS into polymeric micelle (PM) nanoparticles. The half-life of PM encapsulated DS (PM-DS) was extended to over 3 hours in horse serum. The PM-DS showed strong anticancer efficacy. Therefore this nano-enabled DS may be able to translate DS into cancer therapeutics in the future.

Efficient directed migration requires tight regulation of chemoattractant signal transduction pathways in both space and time, but the mechanisms involved in such regulation are not well understood. Here, we investigated the role of protein kinase A (PKA) in controlling signaling of the chemoattractant cAMP in Dictyostelium discoideum. We found that cells lacking PKA display severe chemotaxis defects, including impaired directional sensing. Although PKA is an important regulator of developmental gene expression, including the cAMP receptor cAR1, our studies using exogenously expressed cAR1 in cells lacking PKA, cells lacking adenylyl cyclase A (ACA) and cells treated with the PKA-selective pharmacological inhibitor H89, suggest that PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1 and TORC2. As these pathways control the ACA-mediated production of intracellular cAMP, they lie upstream of PKA in this chemoattractant signaling network. Consequently, we propose that the PKA-mediated regulation of the upstream RasG, Rap1 and TORC2 signaling pathways is part of a negative feedback mechanism controlling chemoattractant signal transduction during Dictyostelium chemotaxis.

A significant racial disparity in breast cancer mortality exists among women in the United States. Triple-negative breast cancer (TNBC) is a breast cancer phenotype that may explain, in part, this disparity between white and African American women. The objective of this study was to determine the predictors of survival in TNBC and non-triple-negative breast cancer (NTNBC) patients. Data on 168,756 female patients with a diagnosis of invasive breast cancer in the Surveillance Epidemiology and End Results (SEER) program were stratified based on breast cancer receptor phenotypes in this retrospective longitudinal cohort study design. Multiple logistic regressions were used for exploring predictors of treatment which showed that not receiving surgery as standard treatment was associated (odds ratio: 95% CI) with TNBC (OR 1.151: 1.042, 1.177), uninsured (OR 3.552: 3.206, 3.937) and African American (OR 1.804: 1.702, 1.912) while not receiving radiation was associated with TNBC (OR 1.151: 1.113, 1.190), uninsured (OR 1.318; 1.217, 1.429). Cox’s hazard models were used, regressing age, race, ethnicity, marital status, health insurance status, histological tumor grade, and treatment status on survival time, the outcome measure. Analysis revealed that the mean survival time is lower for TNBC [15.60 (± 10.29)] months compared with NTNBC [16.01 (± 10.18)] (p < 0.0001), a difference though small is statistically significant. The independent determinants of survival in TNBC were: young age at diagnosis [(β = 0.033, HR 1.033 (1.026, 1.041)]; being African American [(β = 0.182, HR 1.200 (1.117, 1.289)], being married [(β = - 0.362, HR 0.697 (0.658, 0.737)]; higher tumor histological grades [β = 1.034, HR 2.812 (2.159,3.661)]; uninsured [(β = 0.541, HR 1.717 (1.481, 1.992)]; no surgery [(β = 2.156, HR 8.633 (8.152, 9.143)], or no radiation treatment [(β = 0.489, HR 1.630 (1.535,1.73)]. African American race, uninsured status, higher grade at diagnosis, inadequate treatment are independent predictors of poor survival among breast cancer patients; importantly, TNBC had a lower survival than that of NTNBC patients. A higher proportion of TNBC patients had a diagnosis at younger age, with higher tumor grade and was of the African American race. The survival disparity in African American patients may be partially explained by disproportionately higher TNBC cases among them, as well as, rates of not receiving standard treatments.

Production of the glucocorticoid hormone cortisol in response to a stressor is initiated by activation of the hypothalamic-pituitary-interrenal (HPI) axis in fish. Serotonin (5-HT) and negative feedback regulate cortisol production at the whole-animal level; the objective of the present thesis was to investigate their roles in regulating cortisol production by interrenal cells of rainbow trout (Oncorhynchus mykiss). Messenger ribonucleic acid (mRNA) for the 5-HT4 receptor was present in low abundance in interrenal cells. In addition, cortisol production was significantly increased for in vitro head kidney preparations incubated with 5-HT, and this elevated cortisol production was blocked by the 5-HT4 receptor antagonist 5-fluoro-2-methoxy-[1-[2-[(methylsulphonyl) amino] ethyl]-4-piperidinyl]-1h-indole-3-methylcarboxylate sulphamate (GR125487). Thus, 5-HT acts at the head kidney level to regulate cortisol production, probably via the 5-HT4 receptor. Chronic social stress did not appear to regulate the expression of key proteins involved in cortisol biosynthesis or corticosteroid receptors (CR). However, head kidney tissue incubated in vitro with cortisol for 2-8 h showed a reduction in adrenocorticotropic hormone-stimulated cortisol production compared to controls, suggesting the existence of an ultra-short-loop negative feedback mechanism. Thus, the high circulating levels of cortisol in trout experiencing chronic social stress may activate this ultra-short-loop negative feedback mechanism to suppress cortisol production at the head kidney level.

I will bend at a negative impact of transportation to the environment and present alternatives and opportunities to solve actual bad condition.

This thesis is focused on political marketing, especially negative campaign. It describes Parliamentary elections in the Czech republic in 2010 and instruments were used.