[Truncated abstract] A diagnosis of breast cancer is a life-changing event for any woman. For young women and their families it can be devastating. Women aged less than 45 years make up 20% of new cases of breast cancer diagnosed annually in Australia. With the trend for women to delay pregnancy, young women diagnosed with breast cancer may want at least the option to become pregnant after diagnosis and treatment but little is known about how pregnancy affects breast cancer or how breast cancer affects pregnancy. The aims of this thesis were to investigate how concurrent and subsequent pregnancy affects the development and outcomes of breast cancer and how breast cancer affects a concurrent or subsequent pregnancy. This study describes two groups of women identified from the entire Western Australian population less than 45 years of age when diagnosed with: 1. Gestational breast cancer, defined as breast cancer diagnosed while a woman is pregnant or in the first twelve months after completion of a pregnancy; and 2. Breast cancer who subsequently conceive. This study focused on three main areas; patterns of care and outcomes for women diagnosed with gestational breast cancer and those women diagnosed with breast cancer who subsequently conceived; the imaging and pathological characteristics of gestational breast cancer; and lastly the psychosocial issues associated with gestational breast cancer. ... This result was statistically significant. In an age and staged matched case control study lymph node negativity did not purvey a survival advantage for women diagnosed with gestational breast cancer as it did for the non- gestational breast cancer controls. Women diagnosed with breast cancer who have good prognosis tumours need not necessarily wait two years to become pregnant. In an age matched case control study women diagnosed with gestational breast cancer were more likely to have extensive insitu carcinoma, higher mitotic rates and tumours with medullary like features than their age matched controls. In a Cox's proportional hazards regression model which included pathological characteristics, there was no significant difference in survival for women diagnosed with gestational breast cancer were compared to women diagnosed with non-gestational breast cancers. The psychosocial issues for women diagnosed with gestational breast cancer are similar to other young women diagnosed with breast cancer but the effect on the 9 lives of women dealing with pregnancy and breast cancer simultaneously was much greater. The issues of breast cancer and pregnancy are complex at both a physical and psychological level. Much more research is needed to understand the mechanisms of how pregnancy affects breast cancer and its spread. Women who are pregnant when diagnosed with breast cancer or who consider pregnancy after their diagnosis need unbiased support from those around them. Survival is important but other survivorship issues may be just as important. To translate these findings into clinical practice and offer directions for future research eleven recommendations are proposed.

[Truncated abstract] Cardiovascular reflex control of the vasculature is important in maintaining adequate tissue oxygenation in the face of disturbances in physiological homeostasis. Alterations in blood oxygen levels and blood distribution evoke integrated neural, mechanical and humoral responses which modulate peripheral vasomotor tone to maintain systemic cardiovascular integrity. The balance between the local effects of hypoxia and changes in chemoreflex control of vascular tone during hypoxia determine whether net vasoconstriction or vasodilatation is evident in the peripheral vasculature. The mechanisms contributing to hypoxic vasodilatation per se have not previously been defined in healthy humans. Study 1 of this thesis (Chapter 3) investigated the mechanisms contributing to vasomotor responses to chemoreflex activation in the human forearm ... Study 2 (Chapter 4a) investigated the mechanisms controlling vasomotor responses to isocapnic hypoxia in subjects with type 2 diabetes ... Study 3 (Chapter 5) compared the vascular responses to decreased venous return in individuals with and without right atrial afferent innervation ... The results of this thesis indicate that in healthy humans isocapnic hypoxia induces sympathetic vasoconstriction, which masks underlying β-adrenoceptor mediated vasodilatation. The normal vasomotor response to isocapnic hypoxia is impaired in subjects with type 2 diabetes. Despite intact vasoconstrictor responses, subjects with type 2 diabetes exhibited attenuated adrenaline-mediated vasodilatation compared to healthy control subjects, suggesting that the chemoreflex in these subjects is ill-equipped to respond to hypoxic stress. In clinical terms, impaired reflex vasomotor

[Truncated abstract] Therapeutic Radiation has been used for the treatment of cancer and other diseases for nearly a century. Over the past 20 years, Hyperbaric Oxygen Treatment (HBOT) has been used to assist wound healing in the prevention and treatment of the more severe complications associated with the side effects of Therapeutic Radiation Treatment (TRT). The use of HBOT is based on the premise that increased oxygen tissue tension aids wound healing by increasing the hypoxic gradient and stimulating angiogenesis and fibroblast differentiation. As it takes up to 6 months for a hypoxic state to develop in treated tissue, following radiation treatment, current recommendations for HBOT state that it is not effective until after this time. During this 6 month period, immediately following TRT, many specialized tissues in or adjacent to the field of irradiation, such as salivary glands and bone, are damaged due to a progressive thickening of arteries and fibrosis, and these tissues are never replaced. Currently, HBOT is used to treat the complications of TRT, but it would be far better if they could be prevented . . . In summary, this experimental model has fulfilled its prime objective of demonstrating that HBOT is effective in reducing the long-term side effects of therapeutic radiation treatment in normal tissue, when given one week after the completion of the radiation treatment and statistically disproves the Null Hypothesis that there is no difference in the incidence of postoperative complications or morbidity of TRT when 20 intermittent daily HBOT are started one week after completion of TRT. This project provides an extensive description of the histological process and also proposes a hypothesis for the molecular events that may be taking place.

Thesis (M.S.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 40 pages. Includes bibliographical references.

Un bio-marqueur est un paramètre biologique absent ou exprimé à un taux basal en situation physiologique, et présent ou surexprimé en cas d'altération de la fonction tissulaire correspondante. Le dosage de certain bio-marqueurs permet de suivre voire d'anticiper la survenue d'une complication en post-opératoire, et permet la prise en charge rapide et adaptée de cette complication. Les patients opérés cardiaques sont exposés à plusieurs types de complications. Les plus importantes sont l'ischémie myocardique résiduelle voire l'infarctus péri-opératoire, les complications respiratoires, l'insuffisance rénale et les infections de la cicatrice sternale. Chacune de ces complications augmente la morbi-mortalité post-opératoire. Le dosage de la TROPONINE I CARDIAQUE a montré son intérêt dans la détection des ischémies myocardiques résiduelles et le diagnostic d'infarctus péri-opératoire. Nous avons testé l'intérêt du ratio Troponine I cardiaque à 12h / Troponine I cardiaque à 6h dans la détection des ischémies myocardiques résiduelles post-opératoires. Nous avons démontré qu'un rapport de troponine H 12/H6> 1.3 permet de détecter les lésions des greffons au décours de pontages coronariens. Leur détection précoce permet de prévenir l'évolution péjorative des greffons. La NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL), est un marqueur de l'insuffisance rénale jamais encore testé chez les patients insuffisants rénaux chroniques en pré-opératoire de chirurgie cardiaque. Nous avorn démontré que la NGAL plasmatique est un marqueur robuste de l'apparition d'une insuffisance rénale aigüe en post­opératoire de chirurgie cardiaque, chez des patients déjà insuffisants rénaux en pré-opératoire. Un taux de NGAL à la 6ème heure supérieur à l 55ng/ml est un facteur de risque indépendant de survenue d'une insuffisance rénale aigüe post­opératoire. L'ENDOCAN est un marqueur de l'atteinte pulmonaire, qui n'a jamais été testé dans le cadre de la chirurgie cardiaque. Nous proposons de: 1) Déterminer la cinétique de L'Endocan dans le contexte inflammatoire de la CEC, 2) Evaluer le lien entre la diminution du taux d'Endocan circulant et le risque d'évolution vers une défaillance respiratoire d'origine septique ou inflammatoire, 3) Comparer la cinétique de l'Endocan à celle d'autres marqueurs de l'inflammation et de l'infection: Protéine C Réactive (CRP) et procalcitonine (PCT), et 4) Evaluer la valeur pronostique du taux d'Endocan dans la survenue des décès postopératoires d'origine respiratoire. Nous avons réalisé une étude pilote qui a mis en évidence que 6 heures après l'intervention, les patients ayant présenté une infection pulmonaire post-opératoire avaient des niveaux significativement plus élevés d'Endocan que les patients sans infection pulmonaire. Cette étude pilote a montré un intérêt potentiel pour concevoir une étude spécifique, qui a été soumise pour publication. Nous avons réalisé secondairement une étude prospective incluant 155 patients. Les résultats confirment ceux de l'étude pilote à savoir que le taux d'Endocan en préopératoire et à 6 heures est prédictif de l'atteinte pulmonaire post-opératoire. / A biomarker is a biological parameter absent or expressed at a basal Ievel in physiological situation, and present or overexpressed in the event ofalteration of the corresponding tissue function. The dosage ofsome biomarkers makes it possible to follow or even anticipate the occurrence of a postoperative complication, and allows a rapid and adapted management ofthis complication. Patients with heart surgery are exposed to several types of complications. The most important are residual myocardial ischemia and perioperative infarction, respiratory complications, renal insufficiency and sternal wound infections. Each c these complications increases post-operative morbidity and mortality. The determination of the cardiac TROPONINE I has shown its interest in the detection ofresidual myocardial ischemia and the diagnosis ofperioperative infarction. We tested the cardiac Troponin I ratio at 12 h / cardiac Troponin I at 6 h in the detection ofpost-operative residual myocardial ischemia. We have demonstrated that a ratio oftroponin Hl2 / H6> 1.3 makes it possible to detect the lesions of the grafts after coronary bypass surgery. Their early detection makes it possible to prevent the pejorative evolution of the grafts. NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL), is a marker ofrenal failure never tested in patients with chronic renal failure in preoperative cardiac surgery. We have demonstrated that plasma NGAL is a robust marker for the development of acute renal failure in postoperative cardiac surgery in patients with pre-operative renal failure. An NGAL level at the 6th hour above 155ng / ml is an independent risk factor for the occurrence of post­operative acute renal failure. ENDOCAN is a marker ofpulmonary involvement, which has never been tested in cardiac surgery. We propose to: 1) Determine the kinetics ofEndocan in the inflammatory context of the CEC, 2) Assess the Iink between the decrease in circulating endocan and the risk ofprogress towards respiratory failure ofseptic origin or Inflammatory, 3) Compare endocan kinetics with other markers of inflammation and infection: Protein C Reactive (CRP) and procalcitonin (PCT), and 4) Assess the prognostic value of the rate of inflammation, Endocan in the occurrence ofpostoperative respiratory deaths. We conducted a pilot study that found that 6 hours after the procedure, patients with postoperative pulmonary infection had significantly higher levels ofEndocan than patients without pulmonary infection. This pilot study showed a potential interest in designing a specific study, which was submitted for publication. We performed a prospective study, which included 155 patients. The results confirm the results of the pilot study, namely that the preoperative and 6-hour Endocan is predictive ofpostoperative pulmonary involvement

Le placenta est l’organe central de la grossesse et son bon fonctionnement est essentiel pour mener à une grossesse à terme sans complication. L’inflammation joue un rôle très important dans les différentes étapes de la grossesse, de l’implantation à l’accouchement. Lorsque cette inflammation est débalancée au niveau du placenta, cela peut causer plusieurs altérations de ses fonctions. L’inflammation peut être induite par deux différents stimuli, soient par une intervention externe, donc infectieux (via les Pathogen-Associated Molecular Patterns, PAMPs) ou de façon endogène (via les Damage-Associated Molecular Patterns, DAMPs). L’augmentation de l’inflammation est aussi associée avec les complications de la grossesse, qui touchent 5-12% de toutes les grossesses et qui peuvent mener à des conséquences dévastatrices sur la santé de la mère et du nouveau-né. Ces complications comprennent la prééclampsie (PE), l’accouchement prématuré (AP) et le retard de croissance intra-utérin (RCIU). Malgré que ces pathologies aient des étiologies différentes, elles partagent un facteur commun qui joue un rôle essentiel soit, l’inflammation. Dans le but de mieux comprendre le rôle et les effets de l’inflammation sur le placenta humain et dans les complications de la grossesse, nous avons évalué les effets d’un PAMP (LPS) et d’un DAMP (IL-1) classiques dans un modèle d’explants placentaires humains et nous avons réalisé une étude transcriptomique non biaisée de placentas issus de chaque pathologie. Tout d’abord, nous avons démontré que le LPS induisait une plus grande quantité de cytokines pro-inflammatoire comparativement à l’IL-1 et que l’inhibition de la voie de signalisation de l’IL-1 par son antagoniste (IL-1Ra) diminuait leur expression et leur sécrétion. De plus, le LPS induisait une augmentation de la mort cellulaire dans les explants et la prolifération des cellules de Hofbauer, macrophages placentaires. Par la suite, l’étude du transcriptome de placentas provenant de complications de la grossesse (PE, AP et RCIU) a permis de constater que les pathologies ne forment pas de groupes (clusters) basés sur l’expression globale des gènes comparativement placentas issus de grossesses sans complication qui se regroupaient majoritairement ensemble. Il a été possible d’identifier les gènes significativement différents dans chaque pathologie et l’ontologie génique de ceux-ci. Nous avons identifié 198 gènes communs à toutes les complications de la grossesse qui sont majoritairement associés à des processus inflammatoires tels que l’interaction entre les cellules lymphoïdes et non lymphoïdes, l’activation leucocytaire et la régulation de la production de cytokines. Enfin, en plus de confirmer les modulations connues de certains gènes dans chaque complication de la grossesse, nous avons été en mesure d’identifier de nouveaux gènes qui n’avaient jamais été associés avec les pathologies, tels que FUT9, SLAMF7 et TGM3. En conclusion, les travaux présentés dans cette thèse démontrent que l’inflammation induite par le LPS et l’IL-1 n’a pas les mêmes effets au niveau du placenta. L’inflammation est une composante commune aux différentes complications de la grossesse et une meilleure compréhension des processus inflammatoires modulés dans chaque pathologie pourrait permettre le développement de nouvelles approches thérapeutiques. Des travaux futurs pourraient s’intéresser au potentiel prolifératif des cellules de Hofbauer et à l’investigation des nouveaux gènes identifiés par les résultats transcriptomiques. / The placenta is the central organ of pregnancy and its adequate functioning is essential to ensure term delivery without complications. Inflammation plays a key role in every step of pregnancy, from implantation to delivery. When this inflammation is unbalanced in the placenta, it can alter its functions. Inflammation can be induced by two different stimuli, either by external intervention like an infection (with Pathogen-Associated Molecular Patterns, PAMPs), or endogenously (with Damage-Associated Molecular Patterns, DAMPs). Increased inflammation is also associated with pregnancy complications and they affect 5-12% of all pregnancies and can have deleterious effects on maternal and infant health. These complications include preeclampsia (PE), preterm birth (PTB) and intrauterine growth restriction (IUGR). Even if these pathologies have different etiologies, they share a common factor that plays an essential role, inflammation. In order to better understand the role and the effects of inflammation on the human placenta and in pregnancy complications, we have evaluated the effects of classical PAMP (LPS) and DAMP (IL-1) on human placental explant model and we have realized an unbiased transcriptomic study of the placentas from each pregnancy complication. First of all, we demonstrated that LPS induced a higher production of pro-inflammatory cytokines compared to IL-1 and by inhibiting the IL-1 pathway using its antagonist (IL-1Ra), we decreased their expression and their secretion. Moreover, LPS treatment induced more cell death in the explants and proliferation of Hofbauer cells, macrophages of the placenta. Thereafter, transcriptomic study of placentas from pregnancy complications (PE, PTB and IUGR) allowed us to demonstrate that the pathologies were not clustering together based on their global gene expression compared to placentas from uncomplicated pregnancies which the majority of them were clustering together. It was possible to identify genes that were significantly modulated in each pathology and their gene ontology. We identified 198 genes common to all pregnancy complications and they were mostly related to inflammatory processes like interaction between lymphoid and non-lymphoid cells, leukocyte activation and regulation of cytokine production. Finally, in addition to confirming gene modulations previously known in each pregnancy complications, we were able to identify new genes that have never been associated with the pathologies such as FUT9, SLAMF7 and TGM3. To conclude, the work presented in this thesis show that inflammation induced by LPS and IL-1 did not have the same effect on the placenta. Inflammation is a key component to pregnancy complications and a better understanding of the inflammatory processes modulated in every pathology could help the development of new therapeutic strategies. Future work could investigate the proliferative potential of the Hofbauer cells and explore the new genes identified by the transcriptomic results.

Thesis (M. Pharm) -- University of Limpopo, 2019 / Diabetes mellitus (DM) is a major public health problem, challenging patients, healthcare professionals, health planners and policy makers worldwide. Its prevalence has been on the rise for the past four decades, with this trend expected to continue. With this challenge, the management of DM should be done following evidence-based guidelines to prevent or slow down the development of DM-related complications. According to the Society of Endocrinology Metabolism and Diabetes South Africa (SEMDSA) guidelines, it has been shown that strict glycaemic control and proper clinical monitoring can help with prevention and slowing down development of complications. If left untreated or poorly controlled, DM progresses into an array of complications which may increase morbidity and mortality. The prevalence and management of DM complications was investigated. Objectives: • To determine the prevalence of DM complications at Mankweng Hospital. • To evaluate the management of patients with DM complications at Mankweng Hospital. • To determine the factors contributing to the development of complications. • To determine preventive measures taken on non-complicated patients to prevent them from complicating. Method: A retrospective longitudinal review of 134 randomly selected patient records was conducted for a five-year period spanning from June 2012 to May 2017. A pretested DM complications checklist was used to collect data from the patient records. A cross-sectional study was conducted amongst healthcare professionals caring for patients with DM. A total of 41 healthcare professionals were included in the study where a self-administered questionnaire was used to obtain the data. Both sets of data obtained were analysed using IBM SPSS version 25. xiii Results: Retrospective study The study sample population was entirely consisted of African patients with 70.1% (n=94) females and 29.9% (n=44) males. In the sample, 17.2% were suffering from T1DM while 82.8% were suffering from T2DM. The complications with the highest prevalence were diabetic nephropathy, peripheral neuropathy and diabetic retinopathy with prevalence of 35.8%, 32.1% and 22.4% respectively. Vascular diseases, autonomic neuropathy and diabetic foot ulcer had prevalence of 9.7%, 9% and 6% respectively. The overall prevalence of complications in general was 67.2% which was very high. Cross-sectional study A self-administered questionnaire was distributed amongst 41 healthcare professionals (14 males and 27 females). This sample consisted of 9.8% doctors, 41.5% pharmacists, 17.1% professional nurses, 17.1% physiotherapists, 2.4% podiatrists and 12.2% optometrists. It was discovered that only 92.6% and 84.6% of the participants were compliant with the guidelines in terms of random blood glucose tests and blood pressure (BP) per every visit. Only 50% of the HCPs revealed that HbA1c tests should be done according to the guidelines. Merely 5.6%, 8.3%, 5.3% and 22.7% of the HCPs correctly indicated the frequency of foot examinations, eye examinations, renal function tests and lipogram tests respectively, as per the guidelines. Patient related factors were rated as the most contributory factors (56.4%) to the development of complications. Socio-economic and medication related factors had most of the HCPs (36.1% and 29% respectively) rating them as moderate in terms of how much they contribute to the development of complications. The factors rated the least were healthcare team (32.4%) and health system (33.3%) related factors. Conclusion: There was a high prevalence of overall complications in general, with diabetic nephropathy, peripheral neuropathy and diabetic retinopathy being the three highest individual complications. There was poor monitoring of patients with complications as the compliance with the SEMDSA guidelines was very low. Patient related factors xiv were rated the most contributory factors to the development of complications in patients with DM. Recommendations: There is need to implement patient-centred DM care which makes sure that the patient is involved in decision making so that they take responsibility of their own health. There is need for the development and implementation of institutional quality improvement programs where regular audits of the processes of DM care and outcomes are monitored. Limitations: • The limitations of the study are that the researcher completely relied on patient records. • The sample size for HCPs was very small and therefore the study results cannot be generalised. / HWSETA

Indiana University-Purdue University Indianapolis (IUPUI) / Although cancer and treatment-associated cognitive dysfunction has been well-documented in the literature, much work remains to elucidate the biological mechanisms driving this effect, hampering current therapeutic efforts. To address this gap, we first reviewed studies utilizing neuroimaging to characterize cognitive dysfunction in cancer, as studies of neurodegenerative diseases point to neuroimaging as a sensitive measure of cognitive dysfunction. This review highlighted the need for longitudinal imaging studies of cancer and treatment-related changes in cerebral structure and function. Subsequently, we utilized multimodal neuroimaging techniques in a female breast cancer cohort to investigate the longitudinal impact of cancer and chemotherapy treatment on cerebral perfusion and gray matter. Our findings indicate that chemotherapy is associated with elevated perfusion, primarily in posterior brain regions, as well as depressed frontal perfusion associated with decreased frontal gray matter density. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. We also investigated the relationship of cognitive dysfunction and chemotherapy-induced peripheral neuropathy (CIPN), another type of chemotherapy-related nervous system sequelae, again utilizing multimodal, longitudinal neuroimaging, and found that peripheral neuropathy symptoms following chemotherapy were associated with changes in cerebral perfusion and gray matter density. Together, these findings support the hypothesis that multiple biological mechanisms drive cancer and treatment-related cognitive dysfunction. Interestingly, although cancer is associated with cognitive dysfunction, epidemiological studies have shown that cancer and Alzheimer's disease (AD) are inversely correlated. To extend our imaging analysis beyond breast cancer, we leveraged the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to investigate the inverse relationship of cancer and AD and investigate the impact of both of these diseases on gray matter density. We found that though the inverse relationship of these diseases was replicated in the ADNI cohort, cancer history was associated with lower gray matter density, similar to findings from breast cancer studies, independent of AD diagnostic group. Finally, we reviewed microRNA studies, as microRNAs are important regulators of many cell signaling pathways and have been actively investigated in relation to both diseases. This review suggests several pathways that may be driving the inverse association and may contribute to cognitive dysfunction.

Prematurity is a worldwide problem. Every year, 15 million babies are born prematurely, and 1 million of those babies die because of related complications. The surviving premature babies are struggling to hold on to their lives, and even when they do live, most of them end up having various complications to survive and get stronger. There are physical complications faced on their journey such as having underdeveloped lungs, pneumonia, obesity, sepsis, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia, asthma, wheezing, bronchiolitis, cerebral palsy, and motor impairment. They can also develop mental and behavioral health complications such as depression, seizures developmental delay, schizophrenia, autism spectrum disorder, psychological development disorders, behavioral problems, attention problems, and ADHD later in life. The purpose of this systemic review is to understand the impact of long-term complications of premature birth on individual life and society. We hypothesized that based on data from primary research, nearly one half of the infants will have either physical and/or cognitive/developmental health complications. We hypothesized that infants born premature have more physical complications than cognitive complications and infants born prematurely have more cognitive complications than physical complications. This research was carried out by finding cohort study design studies through Medline, Academic Search Premier, and APA PsychINFO, where the studies will be compiled from 2003 – 2020.

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