Multiple lines of evidence suggest that elevated plasma lipoprotein(a) (Lp(a)) concentrations are a significant risk factor for the development of a number of vascular diseases including coronary heart disease and stroke. Lp(a) consists of a low-density lipoprotein (LDL)-like moiety and an unique glycoprotein, apolipoprotein(a) (apo(a)), that is covalently attached to the apolipoproteinB-100 (apoB-100) component of LDL by a single disulfide bond. Many studies have suggested a role for Lp(a) in the process of endothelial dysfunction. Indeed, Lp(a) has been shown to increase both the expression of adhesion molecules on endothelial cells (EC), as well as monocyte and leukocyte chemotactic activity in these cells. We have previously demonstrated that Lp(a), through its apo(a) moiety, increases actomyosin-driven EC contraction which, as a consequence, increases EC permeability. In this thesis, we have demonstrated a role for the strong lysine-binding site in the kringle IV type 10 domain of apo(a) in increasing EC permeability, which occurs through a Rho/Rho kinase-dependent pathway. We have further validated these findings using mouse mesenteric arteries in a pressure myograph system. We also have dissected another major signaling pathway initiated by apo(a) that involves in a disruption of adherens junctions in EC. In this pathway, apo(a)/Lp(a) activates the PI3K/Akt/GSK3β-dependent pathway to facilitate nuclear translocation of beta-catenin. In the nucleus beta-catenin induced the expression of cyclooxygenase-2 (COX-2) and the secretion of prostaglandin E2 (PGE2) from the EC. Finally, we have presented data to suggest a novel inflammatory role for apo(a) in which it induces the activation of nuclear factor-kappaB through promotion of the dissociation of IkappaB from the inactive cytoplasmic complex; this allows the nuclear translocation of NFkappaB with attendant effects on the transcription of pro-inflammatory genes. Taken together, our findings may facilitate the development of new drug targets for mitigating the harmful effects of Lp(a) on vascular EC which corresponds to an early step in the process of atherogenesis. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2009-09-22 19:24:04.594

No description available.

Purpose: To accurately and precisely evaluate the validity and reliability of the English-language Pelvic Floor Inventories (PelFIs) administered questionnaire. Participants: Fifty female patient volunteers (ages 24 to 82 years) plus fifty female control volunteers (ages 21 to 83 years) completed the 149-item questionnaire. Results: Construct validity of the English-language PelFIs was established by quantifying the differences in prevalence of pfm dysfunction between the patient population and the control population. Very significant findings of F=10.83, p<0.0001 were found for the document as a whole. Content validity was attained by experts, and additional information gathered for further improvement of this tool. Test-retest reliability for all domains was established with ICC=0.905 and no significant differences were found between time-one and time-two. Internal consistency was obtained with significant Pearson's Correlation noted between the domains. The prevalence of co-occurrence of pfm disorders with patients presenting for treatment of a single pfm dysfunction was quantified and 100% of the patients reported symptoms in domains additional to the domain they sought treatment for. The presence of pfm dysfunction was also quantified in the control population and 94% were found to display symptoms of pelvic floor dysfunction. Conclusions: The English-language PelFIs was shown to be valid and reliable. Co-occurrence of pfm dysfunction was found to be highly prevalent.

Traumatic brain injury (TBI) is a prominent disease in developed countries, and age is an important factor in functional outcome. Although aged patients typically show diminished recovery compared to young patients, and have higher mortality and morbidity following TBI, the mechanism is not well understood. To date, there is no effective therapeutic for TBI. Previous studies indicate a secondary injury in TBI begins immediately after impact, and is likely the major contribution to delayed neuron dysfunction and loss. Studies also suggest mitochondrial dysfunction and increased free radical species (ROS) production following TBI may play a key role in the process. To evaluate oxidative damage following TBI, especially in aging, young (3 months), middle aged (12 months) and aged (22 months) Fisher-344 rats were subjected to a unilateral controlled cortical impact (CCI) injury, and tissue sparing, 4-hydroxynonenal (HNE) and acrolein levels, and antioxidant enzyme activities, and DNA oxidative damage were measured. In order to evaluate changes in mitochondria following TBI, mitochondrial protein levels were investigated using young adult animals. To evaluate a potential therapeutic for TBI, the effect of creatine on oxidative damage was evaluated. These studies show an age dependent increase of oxidative damage following TBI, demonstrated by increased levels of 4-HNE, acrolein and 8-hydroxyguanine. Middle aged and aged animals showed increased tissue loss compared to young animals 7 days post injury. Mitochondrial proteins involved in the respiratory chain, carrier proteins and channel proteins were significantly decreased 24 h post injury in ipsilateral cortex, but increased in both ipsilateral and contralateral hippocampus. To study potentially protective compounds in TBI, animals were fed with creatine two weeks before TBI and showed less oxidative damage and increased antioxidant capacity, which suggests creatine may be a potential drug for clinical treatment of TBI. The work described in this dissertation is the first to show increased oxidative damage and diminished antioxidant capacity in TBI in aging. The study of mitochondriafollowing TBI using quantitative proteomics is also the first time to show multiple mitochondrial proteins change following TBI. These data are also the first to show creatine can increase antioxidant defenses. These studies contribute to our understanding the mechanisms of secondary injury in TBI in aging.

The purpose of this study was to determine the prevalence of temporomandibular disorders (TMD) in fibromyalgia (FM) patients compared to failed back syndrome (FBS) patients. In addition, the FM and FBS patients were assessed and compared with regard to their psychosocial dysfunction. The study included 51 adult patients (FM = 32, FBS = 19) recruited from a physical medicine and rehabilitation clinic and a FM workshop. Questionnaires included an orofacial pain questionnaire and a battery of psychological questionnaires that included the Symptom Check List-90-Revised, the Pittsburgh Sleep Quality Index, the Multi-dimensional Pain Inventory, the Post-traumatic Stress Disorder Checklist-Civilian Version, and Multidimensional Fatigue Symptoms Inventoryshort form. Each patient underwent a clinical examination by a dentist who was blind to the diagnostic category and if applicable was diagnosed with TMD based on the Research Diagnostic Criteria for TMD. Fifty three percent of the FM patients reported having face pain compared to 11% of the FBS patients (P=0.002). Of those FM patients who reported face pain, 71% fulfilled the criteria for TMD. The psychometric data revealed that the FM patients had higher scores for somatization (P=0.02) and obsessive-compulsive (P=0.009) subscales compared to the FBS patients. The mean score of medication used to sleep was higher among the FM patients compared to FBS patients (P=0.002). Eighty seven percent of the FM patients reported a stressful event (P=0.036). Of those FM patients who reported a stressful event 42.3% were deemed post-traumatic stress disorder positive. FM patient also had higher scores for general fatigue (Pandlt;0.0001), emotional fatigue (P=0.008), physical fatigue (Pandlt;0.0001) and mental fatigue (Pandlt;0.0001) as compared to FBS patients. The high prevalence of TMD and psychosocial dysfunction among FM patients suggests a dysfunctional hypothalamic-pituitary-adrenal axis and dysregulated autonomic nervous system.

I denna uppsats studerar vi delningar av artiklar på det sociala mediet Facebook. Syftet är att undersöka informanternas egna tankar, reflektioner och upplevelser av vad de läser och delar med sig av på Facebook. Det vi vill undersöka är användandet av artiklar som opinionsbildande material - så som krönikor, debattinlägg och nyheter. Fokus ligger på att försöka se hur informanternas förhållande till deras åsikter och värderingar påverkas av vad de läser och delar på Facebook, samt hur och varför de använder sig av delningar. Vi har genomfört sex stycken kvalitativa intervjuer med informanter mellan 25-38 år, både kvinnor och män. De övergripande frågeställningar vi ville besvara var; Varför väljer informanten att läsa artiklar på Facebook? Varför väljer informanten att dela/dela vidare på Facebook? Hur ser relationen ut mellan de delningar informanten gör och informantens åsikter? För analysen har vi främst använt oss av teorierna Uses &amp; Gratifications, som vi hämtat från Lee &amp; Ma (2012), samt Kang et al (2013) för att förklara motivet till delningar och Nyhetsvärdering som baseras på Galtung och Ruge´s kriterier för nyhetsvärdering, för att förklara vad de läser. Vi har även använt oss av Agenda-Setteing och Narcotizing Dysfunction för att närmare kunna förklara motiv, urval och vad resultatet av delningar blir. Resultatet visar att informanterna främst delar för att påverka andra och bidra till samhällsdebatten. Samtidigt så anser de att de inte själva blir påverkade av vad andra delar.

Aims: The primary physiotherapeutic aims of the study were to validate a manual physiotherapy evaluation technique in the assessment of cervical biomechanical dysfunction, and to test the effectiveness of a manual physiotherapy treatment technique in the correction of cervical biomechanical dysfunction. The primary educational aims were to test the effectiveness and safety of a therapeutic exercise programme for the correction of biomechanical dysfunction as well as the effectiveness of a neck rehabilitation programme for improving neck muscle strength. Design: A four group experimental design with three pre-test - post-test groups and a control group was used for the investigation. Sample: The subjects were South African schoolboy rugby players between the ages of 15 and 18 years. Groups I and 2 presented with biomechanical dysfunction of their cervical spines, Group 3 had no biomechanical dysfunction of their cervical spines and the players of Group 4, the control group, presented with or without biomechanical dysfunction of their cervical spines. Each group consisted of 25 players. Method: Group I received manual physiotherapy with x-rays before and after treatment. Groups 2 and 3 performed a therapeutic exercise programme, with before and after x-rays, and Group 4 received no intervention between their sets of x-rays. Following the second set of x-rays all the players from Groups I, 2 and 3 performed the neck rehabilitation programme after which a third set of x-rays were taken. Results: The results validated the manual physiotherapy evaluation technique. The manual therapy treatment technique used in the treatment of Group I showed highly significant improvements in cervical biomechanical function. Results for Group 2 following the therapeutic exercise programme showed moderate practically significant improvements in cervical biomechanical dysfunction. The therapeutic exercise programme for the correction of biomechanical dysfunction was found to be very safe with only small significant changes in x-ray measurements (Group 3). The results of the control group showed a negative trend of small statistical significance. A highly significant improvement in cervical circumference as moderate significant improvement in biomechanical function was found following the neck rehabilitation programme. Conclusion: It could therefore be concluded that the manual physiotherapy evaluation technique for motion segment analysis was indeed valid in determining biomechanical dysfunction of the cervical spine. The manual physiotherapy treatment technique as well as the therapeutic exercise programme for the correction of biomechanical dysfunction was found to be effective in the correction of cervical biomechanical dysfunction. It could further be concluded that the therapeutic exercise programme was safe to be performed by players without biomechanical dysfunction. The neck rehabilitation programme was effective in improving cervical circumference as well as cervical biomechanical function. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2005.

Purpose: To accurately and precisely evaluate the validity and reliability of the English-language Pelvic Floor Inventories (PelFIs) administered questionnaire. Participants: Fifty female patient volunteers (ages 24 to 82 years) plus fifty female control volunteers (ages 21 to 83 years) completed the 149-item questionnaire. Results: Construct validity of the English-language PelFIs was established by quantifying the differences in prevalence of pfm dysfunction between the patient population and the control population. Very significant findings of F=10.83, p<0.0001 were found for the document as a whole. Content validity was attained by experts, and additional information gathered for further improvement of this tool. Test-retest reliability for all domains was established with ICC=0.905 and no significant differences were found between time-one and time-two. Internal consistency was obtained with significant Pearson's Correlation noted between the domains. The prevalence of co-occurrence of pfm disorders with patients presenting for treatment of a single pfm dysfunction was quantified and 100% of the patients reported symptoms in domains additional to the domain they sought treatment for. The presence of pfm dysfunction was also quantified in the control population and 94% were found to display symptoms of pelvic floor dysfunction. Conclusions: The English-language PelFIs was shown to be valid and reliable. Co-occurrence of pfm dysfunction was found to be highly prevalent.

Balance dysfunction and the resultant falls and injuries, loss of confidence, alternations lifestyle and the overall costs are a major problem to older people in Australia. The studies in this thesis investigate discrete but inter-linked aspects of the problems of falls among community dwelling older people, including measurement issues, prediction of fallers, types of dysfunction related to clinical diagnoses, and the effect of multidisciplinary intervention. Preliminary studies of older people from both healthy and clinical samples identified high retest reliability for the dynamic balance tests on the Chattecx Balance System, high retest reliability and concurrent validity for a new clinical test of dynamic standing balance, and high retest reliability and predictive validity for an expanded scale to measure fear of falling. (For complete abstract open document)

Thesis (Ph. D.)--University of Washington. / Bibliography: leaves [120]-123.