D.Cur. (Psychiatric Nursing) / Malawi has a population of 9 million people with AIDS the leading cause of death in the age group of 20 • 40. The HIV prevalence rate, estimated at 23% in urban areas and 8% in rural areas, is one of the highest in the world (AIDSEC, 1994: I). Evaluation of counselling practices showed poor results with counsellors feeling ineffective and inadequate. Patients are mostly tested on medical indication but testing is increasingly refused by patients who do not see the benefit of knowing their HIV status. The counselling practice as it is known in the Western world is a foreign concept for patients living in rural Malawi. The high stigma of AIDS complicates support of the patients. The goal of this research study is to describe a model of counselling that would meet the needs of an AIDS patient in a rural community in Malawi. A qualitative research design that is explorative, descriptive and contextually specific to rural Malawi was used for the study. In order to describe a counselling model it was important to understand the illness experience of HIV reactive patients. The patients are seen in group context congruent with the African culture and therefore the experience of the primary care giver of AIDS patients is also examined. The experience of counsellors of AIDS patients is explored as the other major factor in the phenomenon examined. In the first phase of the study in-depth phenomenological interviews were conducted with identified groups. Focus interviews were conducted with a hundred AIDS patients to identify the needs and resources of the patients and to compile a demographic profile. Focus group discussions were conducted with counsellors for more complete comprehension. Data analysis and a literature control were undertaken. In the second phase of the study theory generation was used in order to develop a counselling model for AIDS patients and guidelines for implementing the model were generated. Based on the results of the analysis the major concept enable was identified as the essence of a model for counselling AIDS patients in rural Malawi.

Obesity is increasing worldwide. The addition of excess calorie intake and unhealthy human behavior leads to also other diseases such as metabolic syndromes and liver disease such as non-alcoholic fatty liver disease. Furthermore, the accumulation of fat triggers specific mechanisms that, if prolonged, can cause tissue damage. For instance, the innate immune system becomes agitated in patients with NAFLD or obesity due to excessive fat accumulation. This leads to inflammation in specific tissues and infiltration of other immune cells. One of the main immune cells are neutrophils, which secrete a protease enzyme called protease neutrophil elastase. Interestingly, there have been studies conducted that have shown that when neutrophil elastase is knocked out in mouse models that mimic NAFLD, there seems to be a protective effect occurring in the body and lessen tissue scarring. A possible explanation, and the aim of this thesis, is to explore if autophagy is regulated and thus plays a role in protecting liver from inflammation and fibrosis. Western blotting approach was used to test this hypothesis. The protein samples that are used are extracted from neutrophil elastase knockout mice that have been fed a high-fat high-fructose diet and compare them to samples from wild-type control mice that have been fed a normal chow diet, high-fat diet, and high fat high fructose diet. The results indicated that potential upregulation of the autophagy pathway in the liver of neutrophil elastase knockout mice and more studies would need before accurately and reliably acknowledging the alternation of the autophagy pathway in the liver from mouse model of NAFLD and when neutrophil elastase is knocked out. / 2023-12-10T00:00:00Z

Alzheimer's disease has become one of the most common diseases jeopardizing the health of the human being. The main pathological feature of AD is the accumulation of Aβ in the brain to form senile plaques. Therefore, it is of great significance to develop new and efficient drugs targeting at amyloid-β for the detection, diagnosis and therapeutics for Alzheimer's disease. Xanthohumol (Xn) naturally presents in hops (Humulus lupulus L). Studies have shown that it has anti-lipoperoxidative, anti-inflammatory, anti-proliferative activities, antiangiogenic and antioxidant effects, which further illustrates its potential therapeutic for AD. However, the bio-incompatibility and blood-brain barrier impermeability of Xanthohumol hindered it in vivo efficacy potential for treating Alzheimer's disease. Thus, we designed and prepared a series of Xanthohumol derivatives, namely, Xn-n, (n = 1-9) and its chalcone derivatives C-n, (n = 1-10) to enhance the desirable physical, biological and pharmacological properties, especially the blood-brain barrier permeability for intervention of AD. As an effective technique for in vivo visualization, Near-infrared fluorescence imaging based on organic small molecule probes has a promising application in the diagnosis of Alzheimer's disease. However, most of the reported imaging probes can only visualize Aβ-plaques but do not have therapeutic potential such as neuroprotection against Aβ induced toxicity. Herein, we designed and synthesized a series of oligomeric Aβ targeted near infrared (NIR) fluorescent probes for the diagnosis and therapeutics of Alzheimer's disease, namely DBAN-SLM, DBAN-SLOH, DBAN-OSLM which showed remarkably effective inhibitory effect on Aβ aggregation, significant neuroprotection effect against the Aβ-induced toxicities, and suppression on Aβ-induced ROS generation. indicating its great promise as a useful theragnostic agent for the early diagnosis and therapy of AD. Dual-modal imaging is an important approach to overcome the limitations of single imaging technology in the diagnosis of AD disease. Therefore, based on the dual-modal, we designed and synthesized the NIR/MR dual-modal detection and theragnostic probes namely Dyad-1, Dyad-2, Dyad-3 and NP@SiO2@F-SLOH. More surprising is that the two NIR/MR dual-modal probes show excellent biological properties, including the ability to inhibit Aβ aggregation to a certain extent, neuroprotective effects on cytotoxicity caused by different forms of Aβ species, blood-brain barrier (BBB) permeability, and high stability. All of these newly designed and synthesized molecules were characterized with 1H NMR, 13C NMR, and HRMS and found to show good agreement with the desired structures. The photophysical properties and biological properties of these novel designed and synthesized fluorescent probe such as UV-vis absorption, fluorescence emission, dissociation constant determined by fluorescence titration, cytotoxicity assay, neuroprotection, and inhibition of Aβ aggregation were investigated

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in severe cognitive impairment and eventually is fatal. In addition to memory loss, AD patients also present with psychosis and emotional psychological symptoms. Neuropathologically, the disease is characterized by aggregation of amyloid-beta protein that accumulates into plaques and hyperphosporylation of tau protein which results in neurofibrillary tangles. Further, neuropathology in AD results in broad neuroinflammation. In recent years, there has been a research focus on novel treatments for AD because current medications have not been particularly effective and have significant side effects. In the current study, we analyzed whether PD340, a novel anti-inflammatory which inhibits the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) would be effective to alleviate behavioral impairments in the 3xTg mouse model of AD. The 3xTg model is unique in comparison to previous rodent models of AD because it express three dementia-related transgenes and demonstrates a clear age-dependent onset of AD pathology. Mice were bred in our animal colony. Beginning at four months of age, a specialized diet was presented to the animals that contained 0, 3, 10, or 25 mg/kg of PD340. At approximately 6 months of age, which is before any neuropathology presents in this model, animals were behaviorally tested on three different tasks: The Barnes maze, which is a test of spatial memory; Prepulse inhibition (PPI), which is a measure of sensorimotor gating and is related to psychosis and cognition; and the elevated T-maze, which is a test of anxiety. Both males and females were tested. Results from Barnes maze testing revealed that females, but not males, administered 25 mg/kg of PD340 demonstrated a significant improvement in spatial bias towards the goal during acquisition. Regarding PPI, there were no sex differences, but groups receiving the 3 or 25 mg/kg dose of PD340 demonstrated significantly improved performance over animals administered the 0 mg/kg dose of PD340 dependent upon the auditory decibel level of the stimulus presented. On the elevated T-maze, there were no significant group differences, demonstrating anxiety is not present at 6 months of age in this model. Behavioral tests will also be performed at 12 and 15 months of age in these animals. However, at 6 months of age, it appears that PD340 is effective in alleviating behavioral deficits related to cognitive impairment in a mouse model of AD. Future work will analyze neuropathology in the hippocampus and prefrontal cortex, two brain areas that degenerate in AD and are important in cognitive function.

Objective: To promote knowledge and awareness about cardiovascular disease (CVD) among women with recent preeclampsia so that this population may develop more accurate perceptions of their personal CVD risk. Design: An exploratory single group, pretest/posttest educational intervention study. Setting: Telephone-based interviews. Participants: Sixty-four women with preeclampsia in the most recent pregnancy completed the study. The sample was predominately African American. Methods: Knowledge about CVD and the study covariates (age, race, parity, income, marital status, education, and history of previous preeclampsia) were measured prior to CVD education. Levels of CVD risk perception were measured both before and after the CVD educational intervention. Intervention: Structured CVD education by telephone. Results: After CVD education, levels of CVD risk perception were significantly higher than at baseline. Conclusion: As an intervention, CVD education provided by telephone served as a practical and effective approach to contact postpartum women with recent preeclampsia and demonstrated effectiveness in increasing perception of CVD risk.

The attachment and/or penetration of animal cells by two strains of Legionella pneumophila was studied in three vertebrae cell lines in vitro . The study focused on (1) differences in attachment and penetration between the two bacterial strains (an environmental isolate, Johannesburg-2, and a clinical isolate, Chicago-8) and between the cell lines (Hep-2, WI-38 and a murine line); (2) effects of L. pneumophila on cell morphology and growth; and (3) the effects of pyruvate and six sugars or sugar derivatives (D-mannose, D-Galactose, D-Glucose, L-glucose, D-fructose, and 2-deoxy-D-glucose).

Currently cardiovascular disease (CVD) is the leading cause of death globally accounting for nearly 17.9 million deaths every year. Studies show that CVD affects men and women differently. A significant increase in CVD incidence is marked by the onset of menopause in women compared to age matched males. A commonality seen in CVD is the use of ꞵ-adrenergic receptors (ꞵ-ARs), as studies have shown that estrogen loss exacerbates the signaling of these ꞵ-AR’s. Changes within this signaling molecule can lead to structural and functional modifications in the heart, including systolic or diastolic dysfunction. This leads to the hypothesis that estrogen loss exacerbates cardiac function with acute sympathetic stimulation and hypertrophy, but prolonged stimulation blunts the sympathetic response. Female mice were ovariectomized (OVX) or underwent SHAM surgery at 2.5 months of age. These mice were treated with isoproterenol (ISO) to simulate chronic sympathetic stimulation for 7, 14, 21 and 28 days continuously through mini osmotic pumps 3 months post ovariectomy. Echocardiography parameters were analyzed using diastolic diameter (DD), systolic diameter (SD), fractional shorting (%FS), and ejection fraction (%EF). Preliminary results showed that %FS and %EF did not change in the OVX and ISO groups compared to SHAM at 7, 14, and 28 days. Similar results were observed in the OVX compared to ISO + OVX groups at 7 days. Even though %FS and %EF did not change, the DD increased at all time points in OVX and ISO groups compared to SHAM. When comparing OVX and ISO + OVX, SD decreased at 14 and 21 days. There is however a significant increase in %FS and %EF at 21 days for all treatment groups. These preliminary results give a better insight to heart function over the course of multiple time points, suggesting that estrogen loss combined with chronic sympathetic stimulation significantly exacerbates the function of the heart.

Cardiovascular disease is a worldwide problem for both men and women and accounts for nearly 17.9 million deaths every year. Cardiovascular disease affects men and women differently and has resulted in more deaths in women since the 1980’s. Estrogen status decreases with age and as women go through menopause, it increases the burden of CVD events. Clinical studies have shown that estrogen can have cardioprotective effects via its receptors. These receptors binding causes pleotropic affects in signaling to maintain cardiovascular homeostasis. There are limited studies on estrogen loss in the aging heart over a continuous span. We therefore examined the effects of estrogen loss and its role in cardiac structure and function over time in female mice. This research was a collaborative project by 25 undergraduate students. Studies have shown undergraduate research to be extremely useful in improving undergraduate students’ analytical, communication, statistical knowledge, and other scientific and laboratory skills (Tan et al., 2022). During this lab, students performed various histological staining methods, analysis of echocardiograms, and animal research. Female mice were ovariectomized at 2.5 months of age or underwent a SHAM (mock) surgery. Echocardiography was preformed to examine the cardiac structure and function at 1, 3, 5, 12, and 18 months post ovariectomy. Hearts were removed at each time point and sectioned at 4µm thick. Cardiac hypotrophy was then assessed by histological staining using Wheat Germ Agglutin and myocyte cross-sectional area was measured of the stained images. There was a significant increase in cardiac hypertrophy in the 1-month versus 18-month SHAM and OVX groups. Also, there was a significant increase in cardiac hypertrophy between the SHAM and OVX groups at 1-month, 3-month, and 5-month OVX. Echocardiography results revealed significant increases in the diastolic (DD) and systolic diameter (SD) for the SHAM and OVX group at 1-month versus 18-month. Percent Fractional (%FS), and Ejection Fraction (EF) were significantly higher in the OVX group versus SHAM at 1, 5, and 18-month time points. This work highlights the impact of prolonged estrogen loss on changes in cardiac structure and function in the aging female heart.

Despite the fact that eight cases of Lyme disease were diagnosed in San Luis Obispo County between 2005-2013, the identity of wildlife hosts serving as sources for tick infection in this region remained unidentified. The primary cause of Lyme disease in the U.S. is the spirochetal bacterium Borrelia burgdorferi sensu stricto, and this agent had not been previously isolated from the region. Borrelia bissettii, a related species that has not been implicated as a common causative agent of Lyme disease, was isolated in small rodents inhabiting coastal scrub and chaparral habitats in a previous San Luis Obispo County study. However, B. burgdorferi was not detected. In northwestern California, B. burgdorferi has been primarily associated with high populations of the tick vector Ixodes pacificus in dense woodlands or hardwood-conifer habitats, particularly in the western gray squirrel reservoir host, Sciurus griseus. My study investigated the role of S. griseus and other associated rodents as potential reservoirs for B. burgdorferi in central coastal California woodland habitats. Rodents were live-trapped at four sites in San Luis Obispo County in oak and mixed woodland. Rodent ear samples were tested for B. burgdorferi genospecies by bacterial culture and PCR. Ticks were collected from captured rodents and surrounding environments and tested by PCR for the presence of Borrelia. Of 119 captured rodents, seven were positive for Borrelia infection (5.9%) and of these, six were positive for B. burgdorferi (5.0%). There were multiple infected rodent species that included two western gray squirrels, three deer mice (Peromyscus maniculatus), and one brush mouse (P. boylii). Borrelia spp. were not detected by PCR from the 81 ticks recovered from the environment and rodents. Here, for the first time, we verify the presence of B. burgdorferi sensu stricto in San Luis Obispo county rodents. However, in contrast to previous Northern California studies, the western gray squirrel may not be the primary reservoir host for B. burgdorferi in this region. Multiple rodent species in oak woodlands may be involved in spirochete maintenance in San Luis Obispo County.

Bones of the cranial vault protect the underlying brain but preserve flexibility to allow brain growth. The edges of skull bones are joined by fibrous sutures, which provide structural support and are the sites of bone growth. Craniosynostosis (CS), premature fusion of bones at the sutures, causes skull deformity and secondary problems in brain development. Bone morphogenetic protein (BMP) signaling is critical in regulating osteoblast differentiation and ossification. Several components of the BMP signaling pathway are associated with increased risk of CS, supporting a central role for BMP signaling in suture formation and development of CS. However, the specific factors involved and disease mechanisms remain largely unknown. To address the gaps in our knowledge, we identified regulatory elements active in skeletal tissues associated with the risk of CS. Briefly, we selected conserved noncoding elements within the genomic regions near the CS risk genes, BMP2 and BMPER (BMP Binding Endothelial Regulator), and performed zebrafish transgenesis to screen for enhancer activities in cranial skeletal tissues. We found multiple enhancers that directed transgene expression consistent with the expression of endogenous bmp2 and bmper genes. Using confocal microscopy, we demonstrated activity of the enhancer, -707BMPER, in cartilage closely associated with developing frontal bones, suggesting its involvement in cranial bone growth, suture formation and the risk of CS. We also performed an enhanced yeast one-hybrid (eY1H) assay to determine the transcription factors that interacted with the identified enhancers, implicating the underlying signaling pathways in regulation of their activity. Compelling human genetic evidence has revealed a role for SMAD6 (mothers against decapentaplegic homolog 6), a negative regulator of BMP signaling, in craniosynostosis. SMAD6 mutations are also associated with cardiovascular abnormalities and nonsyndromic radioulnar synostosis. However, there are significant unanswered questions about the mechanisms linking specific SMAD6 mutations to any of these defects. To create a tractable animal model to address these questions, we used CRISPR targeting to mutate the zebrafish ortholog, smad6a and smad6b. In addition, we developed a zebrafish assay to evaluate the functional consequences of SMAD6 sequence variants, based on the ability of Smad6 to disrupt dorsal-ventral patterning of zebrafish embryos in a dose-dependent manner. We anticipate that the zebrafish assay can provide a convenient approach to verify the disease risk of SMAD6 variants, and that zebrafish lacking smad6 function will be a tractable genetic model to study the role of Smad6 in development.