Hispanics are the fastest-growing minority group in the United States, but they are the most underserved population in terms of access to online health information. The specific aims of this descriptive, correlational study were to examine factors associated with online health information seeking behaviors of Hispanics and to examine the association between online health information seeking behaviors and health behaviors. The study sample (n=4,070) was recruited from five zip codes in the Washington Heights/Inwood community of New York City for the Washington Heights Inwood Informatics Infrastructure for Comparative Effectiveness Research project. Survey data were collected via interview by bilingual community health workers in three settings: a community center affiliated with Columbia University, households and other community settings, and NewYork-Presbyterian Ambulatory Care Network clinics. Data were analyzed using logistic and linear regressions. In regards to survey respondents' situational, sociodemographic, and literacy factors (health literacy, computer literacy) associated with their online health information seeking behaviors and those of their household members, the study found that that worse health status (OR=0.42, p less than 0.001), lack of hypertension (OR=0.60, p less than 0.01), a high level of education (OR=3.04, p less than 0.001), and computer literacy (OR=3.78, p less than 0.001) were positively associated with respondents online health information seeking behaviors. Health literacy was only positively associated (OR=2.13, p less than 0.001) in a subsample of respondents (n=2,680) in which it was measured by one item related to understanding written health information. Respondents' factors significantly associated with online health information seeking by household members were: female gender (OR=1.60, p less than 0.01), younger age (OR=0.75, p less than 0.01), married (OR=1.36, p less than 0.01), higher education (OR=1.80, p less than 0.001), higher computer literacy (OR=2.24, p less than 0.001), in worse health status (OR=0.592, p less than 0.001), and presence of serious health problems (OR=1.83, p less than 0.01). Controlling for factors found to be significant in Aim 1, respondents' online health information seeking behaviors were hypothesized to be positively associated with fruit consumption, vegetable consumption, physical activity, and hypertension medication adherence and negatively associated with alcohol consumption. Hypotheses related to fruit consumption (p less than 0.05), vegetable consumption (p less than 0.05), and physical activity (p less than 0.01) were supported. This study contributes to the understanding of Hispanics' online health information seeking behaviors and provides the foundation for informatics and public health interventions.

Concerns about the quality of care in nursing homes (NHs) have continued to stimulate research and debate over the past several decades. Although substantial improvements in NH care have taken place, serious challenges remain. With enactment of the Patient Protection and Affordable Care Act (PPACA) and recent NH Value Based Purchasing Demonstrations through the Centers for Medicare and Medicaid Services (CMS), there has been increasing policy interest to efficiently reduce potentially avoidable resident adverse outcomes and costs. Organized into three separate studies, this dissertation explores the comparative and cost-effectiveness of improving NH quality outcomes. The significance and current challenges surrounding NH care quality is discussed in the First Chapter. To gain understanding of current infection prevention interventions conducted in NHs, a systematic literature review was conducted and is presented in Chapter Two. The Third Chapter reports on quantitative findings of NH infections as a function of resident quality and tested variations in nurse workforce characteristics. The Fourth Chapter reports on an economic analysis evaluating the implications of retaining a skilled nursing workforce in NHs. Finally, the Fifth Chapter synthesizes the findings from the previous chapters and serves as the concluding chapter of the dissertation.

No abstract.

This study examined nutritional status and fecundity of women and was approved for patient enrollment by the ETSU Institutional Review Board (IRB). Once enrolled, participants filled out two food frequency questionnaires (FFQ, fruit/vegetable intake, fat intake), self-reported anthropometric data, and had one 5 mL vacutainer of whole blood (EDTA) collected for measures of oxidative stress (OS), coenzyme Q10 level, and fatty acid profile of the red blood cell (RBC) membrane. Participants were either designated to the case group (13 women experiencing fertility problems and an anti-mullerian hormone level of 1 ng/ml or less (AMH, <1 ng/mL)) or the control group (13 women experiencing normal ovulation cycles and no evidence of polycystic disease). This study hypothesized that the case group would have poorer plasma antioxidant status, consume more dietary saturated fat and have lower levels of omega-3 and higher levels of omega-6 fatty acids in the RBC membrane. Results showed that case participants had significantly higher body mass index (BMI) when graduating from high school, BMI upon enrollment in the study, and trended to gain more weight since high school. Antioxidant status of the plasma tended to be higher for the case group. This result was surprising as case participants consumed significantly fewer servings of fruits and vegetables (sources of antioxidants) than control subjects. FFQ results indicated that case participants consumed significantly higher amounts of total fat (g), saturated fat (g), unsaturated fat (g), and their diets had a higher dietary fat percent. No significant differences were noted in the individual fatty acids isolated from the RBC membrane or in calculated ratios of fatty acid between case and control groups. The fatty acid profile from RBC membranes are in agreement with self-reported fat intake from FFQ data and may provide a rationale for no differences observed between the two groups.

Gastrointestinal nematode (GIN) infections affect production systems and exotic hoofstock in zoos, particularly giraffe (Giraffa camelopardalis). Anthelmintic resistance (AR) prevalence is increasing in production systems and zoos. To combat the AR that compounds GIN problems, alternative control methods are used. One such alternative is copper oxide wire particles (COWP), which control the abomasal nematode Haemonchus contortus. COWP was given to seven adult giraffe at Busch Gardens Tampa, at descending dosages: 25 g, 12.5 g, 6.3 g. Treatment administration time was determined by fecal egg count (FEC) being above 600 eggs per gram (EPG), and therefore varied with each animal. FEC following 25 g COWP treatment significantly (p < 0.05) decreased between Week 0 and Weeks 2-5. FEC following 12.5 g COWP treatment significantly (p < 0.05) decreased between Week 0 and Week 2. FEC following 6.3 g COWP treatment showed no reduction between Week 0 and all PT samples. A 25 g COWP treatment was an acceptable part of a GIN control program for treatment of Haemonchus in giraffe, a 12.5 g COWP treatment was minimally acceptable, and a 6.3 g COWP treatment was ineffective. To determine the mechanism of action for COWP, 11 Suffolk lambs were abomasally fistulated and inoculated with H. contortus larvae. Abomasal contents, nematodes, feces, and blood were collected at 0, 12, 36, 60, and 84 hours post-treatment (HPT). pH was measured and nematodes were viewed using scanning (SEM) and transmission (TEM) electron microscopy and energy dispersive x-ray spectroscopy (EDS), and copper content analysis was performed. FEC and packed cell volume (PCV) were determined for each time period. pH was inconclusive. FEC decreased throughout the study and up to 33 days PT; no statistics were performed due to removal of nematodes. PCV had no substantial change, but the study time period was too short for a significant change. SEM showed no obvious changes between pre- and post-treatment. TEM showed cuticle damage present in PT samples. EDS showed copper present in 10 of 11 spots on PT samples. Copper content of nematodes was maximum at 60 HPT. Evidence suggests COWP has a direct effect on H. contortus.

Herpes simplex virus type 1 (HSV-1) is a DNA virus that is a ubiquitous pathogen of humans. The hallmark of the HSV-lifecycle is infection of a mucosal surface with spread to sensory neurons where the virus establishes a latent infection with periodic recurrences for the life of the host. The most common course of symptomatic disease with HSV-1 is the typical mucocutaneous lesion that is self-limiting. HSV-1 can also cause acute encephalitis and ocular pathology on reactivation. Both of these manifestations of the disease have severe consequences. Although ocular infection is less frequent, the extensive prevalence of HSV makes it one of the most common infectious causes of blindness in developed countries. Herpetic encephalitis causes significant morbidity and mortality, particularly in the immunosuppressed or untreated individual. HSV-1 specifies at least 11 glycoproteins that are expressed in the infected cells. The viral glycoproteins are the first interface of the virus with a host cell and are therefore vitally important to virus pathogenesis. Glycoproteins B, C, D, H, and L have been extensively studied and found to be involved in initial attachment, fusion, and entry of the virus into a host cell. Recent work in this laboratory has shown that glycoprotein K (gK) is also involved in the fusion machinery of the virus, however, little was known about the role of gK in the pathogenesis of the virus. To assess the role of gK in pathogenesis, mutant viruses were used an experimental infection in a mouse eye model. In this investigation, gK was found to have a critical role in the pathogenesis of the virus in the eye as well as in spread of the infection to neurons and subsequent development of latency. Following this work, a primary neuronal culture system was established to further define the role that gK played in neuronal infection and transport. Using this system, gK was found to be a critical determinant for neuronal transport and pathology. Since gK deficient viruses appear unable to infect neurons, defining this phenotype may assist in the eventual development of a successful vaccine strain of the virus.

Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illnesses worldwide. As crucially important emerging pathogens, they have caused multiple, notable epidemics of human disease and unnoticed epizootics over recent decades. Despite the public health relevance, very little is known about the geographic distribution of the agents and vectors, relative impact, and risk factors associated to the arboviral infection in many regions of the world and in the tropics in particular. Presented in this dissertation is an experimental study that explores the serology screening of serum samples from 151 patients whom were diagnosed with undifferentiated febrile illness in Sierra Leone, after ruling out endemic malaria and Lassa fever. Related to the laboratory results of the testing, three exploratory experiments on Koutango virus were developed. The experiment directed special interest into the vector mosquito Aedes aegypti and its ability to uptake, disseminate, and transmit the virus. The study of the early events occurring during the interaction between the virus and cells performed in the laboratory was another area of interest with the objective to predict the disease outcome. In order to explore the vertebrate viremia profile, we attempted to develop a suitable animal model for the Koutango virus study in the laboratory. The overall hypothesis of this research is that arboviruses circulating in West Africa are the cause of undiagnosed febrile illnesses. To investigate the hypothesis, this research explores the poorly understood epidemiological features and geographic range of certain endemic arboviruses, particularly the Koutango virus, and whether or not they circulate in the region with the Aedes aegypti mosquito being the competent vector that transmits the virus. The research in this dissertation contributes to the understanding of the epidemiological features and the actual expanding geographical range of many arboviruses. It describes the gold standard laboratory technique for the serology diagnostic of diverse arboviral diseases. In addition, it explores novel laboratory research techniques that may serve as an important tool for the implementation of effective surveillance programs necessary to explore and control the circulation of diverse arboviruses, particularly those associated with human illnesses in West Africa.

West Nile virus (WNV) is one of several flaviruses known to infect mammalian species, including humans. There were 15,257 horse cases reported in 2002 and 1,086 in 2006 in United States. Recently, significant increases in equine and human cases have been reported in United States. Domain III of the WNV envelope protein binds to cellular receptors, and induces a significant portion of the neutralizing antibody response against the virus. CD40 Ligand (CD40L, CD154) enhances productive interactions between T cells and APC and has been shown to function as a potential adjuvant. In this study, we constructed and expressed a fusion protein consisting of the Domain III of WNV envelope protein fused in-frame with the soluble portion of the equine CD40L. Immunizations of rabbits revealed that the recombinant protein induced antibody that specifically reacted with the WNV and neutralized the virus. Similar experiments were performed with horses. Western immunoblots confirmed that vaccinated horses produced antibodies that specifically reacted with the recombinant WNV E DIII proteins. The recombinant DIII protein with TiterMax or CD40L or both as adjuvant(s) induced significantly higher anti-WNV E DIII antibody activities than control and DIII alone groups after first vaccination. The recombinant DIII-CD40L protein vaccine continually induced the anti-WNV E DIII antibody activities without the adjuvant TiterMax. Moreover, the groups immunized with DIII-CD40L+TiterMax and DIII-CD40L showed stronger neutralization activities from week 8 than the other groups, and they maintained the high titers for at least 10 weeks. The results showed that healthy horses vaccinated with recombinant WNV E DIII protein with equine CD40L demonstrated an antigen specific humoral immune response. The responses were enhanced by booster vaccination. Vaccination with this recombinant WNV E DIII-CD40L protein induced a WNV specific immunity in healthy horses that might contribute to protection from WNV-associated disease. CD40L could be utilized as a non-toxic, alternative adjuvant to boost the immunogenicity of subunit vaccines in horses.

Bacterial pneumonia and sepsis are two important causes of mortality in the world. Emergence of multidrug resistant bacteria has necessitated the development of new treatment and/or prevention strategies to augment host immune defense. In this context, the innate host defense is critical in clearing pathogenic bacteria from the host. Early neutrophil recruitment is a critical step in a multistep requence leading to bacterial clearance. Pattern recognition receptors (PRRs) play a critical role in the innate immune system. Receptor interacting protein 2 (RIP-2) is an adaptor for the nod-like receptors (NLR) NOD1 and NOD2. Nucleotide oligomerisation domain 2 (NOD2) is an intracellular PRR that is shown to be important for host defense against intracellular bacterial pathogens. However, the role of NOD2 and RIP-2 during Gram-negative bacterial pneumonia and polymicrobial sepsis has not been explored. Thus, we hypothesize that the NOD2/RIP-2 axis is critical for host defense during bacterial pneumonia and sepsis/septic peritonitis. To test this hypothesis, we infected NOD2(NOD2-/-), RIP-2(RIP-2-/-) deficient mice intratracheally (i.t) with E. coli (106 CFUs/mouse) and Klebsiella pneumoniae (103 CFUs/mouse). We observed that NOD2/RIP2 signaling is critical for the host defense during gram-negative pneumonia and poly microbial sepsis. The NOD2/RIP2 axis regulates neutrophil recruitment via IL-17A production. We also found that NOD2/RIP-2 signaling is essential for the production of IL-6 and activation of STAT3. We demonstrated that RIP-2 regulates inflammasome activity that is independent of NOD2 signaling. Taken together, these data demonstrate that the NOD2/RIP-2 axis plays a critical role in neutrophil-mediated host defense through IL-17A production and by inflammasome activation. In cecal ligation puncture (CLP) induced sepsis, RIP2-/- mice show increased mortality with higher bacterial burden in the peritoneum and systemic organs compared to WT controls. We found reduced neutrophil influx IL-17A and IL-1beta levels in the peritoneum of RIP2-/- mice after CLP. Furthermore, we also observed increased systemic inflammation accompanied by vital organ damage in the knockout mice. As a whole our data suggest a critical role of RIP2 in neutrophil recruitment, along with IL-17A and IL-1beta during sepsis.

Spotted fever group (SFG) Rickettsia are obligate intracellular bacteria that are carried by ticks. One such tick, Dermacentor variabilis is a vector for the etiologic agent of Rocky Mountain spotted fever, R. rickettsii. These ticks also carry a non-pathogenic R. montanensis, the agent used in this study. Interestingly, field data collected from infected D. variabilis throughout the United States revealed that the majority of Rickettsia in ticks are non-pathogenic species such as R. montanensis. Although ticks serve as both vector and reservoir hosts for SFG Rickettsia, many questions regarding tick-Rickettsia interaction remain unresolved. Therefore, the overall goal of this research was to study the relationship between ticks and Rickettsia, specifically examining the molecular mechanisms of rickettsial infection of tick host. As SFG Rickettsia can move between vertebrate and invertebrate hosts, the hypothesis is that conserved mechanisms are utilized for invasion of both types of host cell. Biochemical inhibition assays revealed that the tick molecules, PI 3-kinase, protein tyrosine kinases, Src, FAK, Rho GTPase Rac1, N-WASP, Arp2/3 complex, actin, and V-ATPase are important for R. montanensis invasion. Further studies were executed to molecularly and functionally characterize the tick molecules, Arp2/3 complex and V-ATPase, which are central to rickettsial internalization. Full length cDNA of Arp2/3 complex subunits and V-ATPase from D. variabilis were isolated. Transcriptional profiles of Arp2/3 complex subunits and V-ATPase showed greater expression of the mRNA in tick ovaries compared to midgut and salivary glands. In addition, to gain insight into rickettsial invasion in nature, Arp2/3 complex inhibition assays were performed in tick tissues. The results demonstrated the involvement of Arp2/3 complex in rickettsial entry into midgut, ovary, and salivary glands. The tick molecules identified in this study may provide novel points of intervention in the transmission of tick-borne rickettsial diseases.