By 2030 major depression is predicted to be the leading cause of disease burden in the world; as such, it is critical to understand factors that contribute to the development of depression. The social signal transduction theory of depression hypothesizes that adversity and social threat upregulate pro-inflammatory biomarkers leading to depression. The current study examined whether pro-inflammatory biomarkers (interleukin-6, interleukin-8, c-reactive protein, and tumor necrosis factor alpha) mediate the association between various types of childhood maltreatment (physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect) and adult depression symptoms in a sample of 740 adults (372 female; Mage= 51.6 years, SD = 13.6) who provided retrospective report of childhood maltreatment as part of the Midlife in the United States (MIDUS) Refresher Biomarker study. Additionally, it explored whether these relations differ for males versus females. A series of linear regression analyses were run in SPSS; separate models were run for each form of childhood maltreatment and for interleukin-6, interleukin-8, c-reactive protein, and tumor necrosis factor-alpha. The results showed that childhood maltreatment is a robust predictor of adulthood depression; however, this association did not differ between biological sexes. In addition, only interleukin-6 was shown to partially mediate the association between childhood maltreatment and adulthood depression. These findings highlight the need to explore the use of interleukin-6 to screen for depression in youth. / M.S. / By 2030 major depression is predicted to be the leading cause of disease burden in the world; as such, it is critical to understand factors that contribute to the development of depression. It has been hypothesized that adversity and social threat activate pro-inflammatory biomarkers, which are proteins that can detect inflammation in the body, leading to depression. The current study examined whether several pro-inflammatory biomarkers explain the association between several types of childhood maltreatment (physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect) and adult depression symptoms in a sample of 740 adults (372 female; Mage= 51.6 years, SD = 13.6) who provided report of past experiences of childhood maltreatment. Additionally, it explored whether these relations differ for males versus females. The results showed that childhood maltreatment is a robust predictor of adulthood depression for males and females. Of the inflammatory biomarkers examined, only interleukin-6 was shown to partially explain the association between childhood maltreatment and adulthood depression symptoms. These findings highlight the need to explore the use of interleukin-6 to screen for depression in youth.

Objectives: To assess the expression of the symptoms of jaw muscle pain and its association with alterations in biochemistry, other symptoms and the carriage of staphylococci. Methods: Three different study populations were assessed. The first was selected and examined by the author and consisted of 43 pain and 41 age and sex matched controls. The second was a study of CFS patients who were blinded to the author and the author subsequently examined the associations between jaw muscle symptom reporting and the standardised biochemistry measures. The third study was also blinded to the author but included an investigation of staphylococci and certain cytokine and biochemistry measures. Results: The three studies clearly establish an association between the carriage of toxicogenic coagulase negative staphylococci and the expression of jaw muscle pain in both males and females. These associations were homogeneous and were found whether the patients were selected on the basis of having jaw muscle pain or selected from within a population of patients selected on the basis of having Chronic Fatigue Syndrome. The studies associated the changes with variations in biochemistry and these were in turn associated with symptom expression within the jaw muscle pain patients. These biochemical alterations included the dysregulation of immune cell counts, cytokines, electrolyte and protein metabolism. These symptoms and biochemical changes were associated with pain severity and illness duration and staphylococcal toxin production. From the data a model was developed which shows the mechanisms involved in the development of chronic pain in the jaw muscles. Conclusions: The carriage of toxicogenic coagulase-negative staphylococci were found to be associated with the expression of jaw muscle pain and the alterations in biochemistry associated with these symptoms.

Objectives: To assess the expression of the symptoms of jaw muscle pain and its association with alterations in biochemistry, other symptoms and the carriage of staphylococci. Methods: Three different study populations were assessed. The first was selected and examined by the author and consisted of 43 pain and 41 age and sex matched controls. The second was a study of CFS patients who were blinded to the author and the author subsequently examined the associations between jaw muscle symptom reporting and the standardised biochemistry measures. The third study was also blinded to the author but included an investigation of staphylococci and certain cytokine and biochemistry measures. Results: The three studies clearly establish an association between the carriage of toxicogenic coagulase negative staphylococci and the expression of jaw muscle pain in both males and females. These associations were homogeneous and were found whether the patients were selected on the basis of having jaw muscle pain or selected from within a population of patients selected on the basis of having Chronic Fatigue Syndrome. The studies associated the changes with variations in biochemistry and these were in turn associated with symptom expression within the jaw muscle pain patients. These biochemical alterations included the dysregulation of immune cell counts, cytokines, electrolyte and protein metabolism. These symptoms and biochemical changes were associated with pain severity and illness duration and staphylococcal toxin production. From the data a model was developed which shows the mechanisms involved in the development of chronic pain in the jaw muscles. Conclusions: The carriage of toxicogenic coagulase-negative staphylococci were found to be associated with the expression of jaw muscle pain and the alterations in biochemistry associated with these symptoms.

Cardiovascular diseases are a broad group of diseases, such as heart attack and heart failureaffecting the cardiovascular system. The primary cause of cardiovascular diseases isatherosclerosis, and its progression is brought about by oxidative stress and a complex chronicinflammation reaction cascade. Of central importance are proinflammatory cytokines, regulatedby multiple factors, including interleukin (IL) 17A. This project aims to investigate the effectof IL-17A on the inflammatory response of human vascular endothelial cells by quantifyingchemokine C-X-C motif ligand-1 (CXCL1) release when exposed or not to otherproinflammatory mediators such as TNF-𝛼, IL-6 and IL-1β. To investigate this, humanumbilical cord endothelial cells were cultured and then stimulated with IL-17A alone or incombination with other cytokines, namely IL-6/sIL6R, IL-1β, or TNF-𝛼. After an appropriateincubation time following the stimulations, the supernatants of the cells were collected, and theamount of CXCL1 was analysed with ELISA or qPCR, respectively. At a lower concentration(10ng/ml), IL-17A failed to induce a significant level of CXCL1 release from endothelial cells.However, IL-17A + TNF-𝛼 (5ng/ml) greatly enhanced, higher than inductions from individualtreatments combined, level of CXCL1 release from endothelial cells. Furthermore, combiningIL-17A with IL-1β or IL-6 induced non-abundant and abundant upregulation in CXCL1 release,respectively. On transcription level, the amount of CXCL1 mRNA induced by IL-17A alonewas non-significant, but stimulation with TNF-𝛼 and IL-17A + TNF-𝛼 induced significantlyupregulated expression of CXCL1. In conclusion, we found that IL-17A induced synergeticrelease of CXCL1 in human vascular endothelial cells with TNF-𝛼. In addition, the synergisticimpact of IL-17A and TNF-𝛼 in terms of CXCL1 induction in vascular endothelial cells wasevident on a transcriptional level. Our data imply that combined blockage of IL-17A and TNF-𝛼 could have an enhanced therapeutic effect on vascular inflammation.