Bacteria secrete and sense extracellular signals from neighboring members of a colony in a phenomenon called quorum sensing. These signals vary from species to species but allow for changes in the behavior of a colony based on changes to cell density, environment, or nutrient supply. Of particular interest to human health is the quorum sensing system of Streptococcus pneumoniae as this pathogen accounts for around one million infection-related deaths per year and is difficult to combat largely due to its ability to form biofilms. These polysaccharide coverings protect entire bacterial colonies from antimicrobial agents as well as allow them to adhere well to the nasopharynx passages of organisms, making them hard to remove. To gain a better understanding of quorum sensing in S. pneumoniae, we propose experiments to study its biofilm formation and its interactions with black carbon, a biochar shown previously to interact with the quorum sensing systems of related bacteria species. We hypothesize that inhalation of black carbon will aggravate a S. pneumoniae infection by promoting biofilm-forming quorum sensing systems making it easier for this bacteria to adhere to and remain on mammal lungs. We propose to first explore the competency and biofilm quorum sensing systems in S. pneumoniae to identify any shared signals between the two using RT-PCR and FITC-Dextran experiments. Further experiments will analyze black carbon particles’ effects on bacterial colonies grown on plates and present on the lung linings of mammals.

Dementia is a major public health problem worldwide. Emerging research indicates that clinical infections and PTSD could be important risk factors for dementia. However, evidence for infections and the risk of dementia primarily examines central nervous system (CNS) infections. Extant epidemiological evidence for systemic bacterial infections and the risk for dementia is limited while that for PTSD and the risk for dementia did not account for psychotropic medications commonly used in management of PTSD and could affect cognitive function. The purpose of this study was to 1) review the evidence for CNS infections as possible causes of Alzheimer’s disease (AD) dementia, and 2) using nationwide Veterans Health Administration databases, conduct original retrospective cohort analyses in nationally representative samples of U.S. veterans aged 56 years and older to determine the associations between systemic bacterial infections, PTSD, and psychotropic PTSD medication use with the risk for developing dementia. Review of the research pertaining to an infectious AD etiology hypothesis including the various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD, and the concordance between putative infectious agents and the epidemiology of AD showed evidence linking AD to an infectious cause to be largely inconclusive; however, the amount of evidence suggestive of an association is too substantial to ignore. Analysis of the associations between systemic bacterial infections and the risk for dementia showed a significant association between exposure to any systemic bacterial infection and an increased risk for dementia (hazard ratio [HR] = 1.20; 95% confidence interval [CI] = 1.16-1.24) after adjustment for demographic characteristics, and medical and psychiatric comorbidity. In addition, septicemia (HR=1.39; 95%CI=1.16-1.66), bacteremia (HR=1.22; 95%CI=1.0-1.49), osteomyelitis (HR=1.20; 95%CI=1.06-1.37), pneumonia (HR=1.10; 95%CI=1.02-1.19), UTI (HR=1.13; 95%CI=1.08-1.18), and cellulitis (HR=1.14; 95%CI=1.09-1.20) were independently associated with significantly increased risk of developing dementia after adjustment for potential confounders. Analysis of the associations between PTSD and psychotropic PTSD medication use with the risk for dementia showed a significant association between PTSD and the risk for dementia (HR=1.35; 95%CI=1.27-1.43) after adjustment for demographic characteristics, medical and psychiatric comorbidity, and health care utilization. Analysis of the impact of psychotropic PTSD medications including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), benzodiazepines (BZA), novel antidepressants (NA) and atypical antipsychotics (AA) on the association between PTSD and the risk for dementia showed significant interactions between PTSD and use of SSRIs (p<.0001), NAs (p=.0016), and AAs (p<.0001). Multivariate analysis showed a significant association between PTSD and an increased risk for dementia among individuals not using any psychotropic PTSD medications at baseline (HR=1.70; 95%CI=1.58-1.82). PTSD patients using SSRIs (HR=2.10; 95%CI=1.82-2.41), NAs (2.19; 95%CI=1.94-2.48) or AAs (4.56; 95%CI=4.04-5.15) were significantly more likely to develop dementia compared to those without PTSD and not using any psychotropic PTSD medications. PTSD patients using SSRIs (HR=1.24; 95%CI=1.08-1.42), NAs (HR=1.29; 95% CI=1.14-1.46) or AAs (HR=2.69; 95%CI=2.38-3.04) were also significantly more likely to develop dementia compared to those with PTSD and not using any psychotropic PTSD medications. SNRI (HR=1.35; 95%CI=1.26-1.46) and BZA drug use (HR=1.40; 95%CI=1.35-1.45) at baseline was associated with an increased risk for dementia regardless of PTSD diagnosis. These findings indicate; 1) evidence for an infectious AD etiology hypothesis in inconclusive, 2) both severe (e.g. sepsis), and less severe (e.g. cellulitis) systemic bacterial infections are collectively and independently associated with an increased risk of dementia among older U.S. veterans hence prevention of systemic bacterial infections could positively influence the risk for dementia among older adults, and 3) PTSD and psychotropic medication use are associated with an increased risk for dementia among U.S. veterans. Further epidemiologic, clinical, and basic science research is required to elucidate the mechanisms and the associations between infections and the risk for dementia and to determine if the independent and effect modifying impacts of psychotropic PTSD medication use on the risk for dementia are related to differences in PTSD severity, other psychiatric comorbidity, or whether psychotropic PTSD medication use is an independent risk factor for dementia.

Methicillin-Resistant Staphylococcus aureus (MRSA) began as a nosocomial infection due to overuse of antibiotics. Several previous studies have reported an increase in this infection in adult patients who have not been hospitalized. It has also been reported that there is an increase in MRSA in children. Some of these children became infected even though they were not at high risk for the infection. After approval from the All Children's Hospital Institutional Review Board (IRB), a cross sectional study was conducted with pediatric admissions and pediatric emergency room visits to determine the characteristics of Methicillin-Sensitive Staphylococcus aureus and MRSA. During this study, a review of 672 medical charts was conducted. The study participants ranged in age from newborns to 18 years of age. In order to be enrolled in the study, the subjects' cultures were collected either as outpatients or within 72 hours of admission. The data that was collected from each chart included age, race/ethnicity, gender, type of infection, preexisting medical conditions, and risk factors for infection. The potential risk factors include antibiotic use, previous surgery or outpatient procedure, previous MRSA infection, immunotherapy, community worn device, and residence in a facility. Statistical analysis was conducted using Epi Info and SAS software packages. In regards to demographic characteristics, black children are 2.98 times more likely to have an MRSA infection than white children. Gender and age were not risk factors for the development of the infection. The risk factors that were significant in whites were home health care (OR= 6.12, CI= 5.16, 7.08), community worn device (OR= 2.28, CI= 1.67, 2.89), previous hospitalization (OR= 2.43, CI= 1.95, 2.91), previous MRSA infection (OR= 3.69, CI= 2.90, 4.48), and previous surgery (OR= 2.02, CI= 1.51, 2.53). In blacks, females were more likely to have MRSA (OR= 2.57, CI= 1.73, 3.41). This finding may be due to the small sample size of black children in the study. Of the analyzed risk factors, home health care (OR= 2.95, CI= 1.11, 4.79), community worn device (OR= 2.85, CI= 1.71, 4.01), previous hospitalization (OR= 1.98, CI= 1.13, 2.83), previous surgery (OR= 2.79, CI= 1.79, 3.79), and previous antibiotic (OR= 5.60, CI= 4.66, 6.54) use were all significant risk factors in blacks. Effect modification was tested between race and all risk factors. Race was an effect modifier only for the risk factor of previous antibiotic use (pvalue =.02). Adjustment of confounding was performed for each race due to the presence of effect modification. After the adjustment for confounding in whites, only home health care (OR=4.37 CI= 1.55, 12.32), previous MRSA infection (OR= 2.86 CI= 1.16, 7.05), and previous hospitalization (OR= 2.00 CI= 1.14, 3.50) remained statistically significant. In blacks, after adjustment of confounding, only previous antibiotic use (OR= 5.13 CI= 1.75, 15.08) remained significant. Adjustment for confounding was also preformed on the total risk factors model. A dose response relationship was present with increasing risk factors present.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2010.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Lyme disease is one of the most common infectious diseases present in the United States today and it is clear that the changing climate will affect the geographical range of it across the country. Climate change may impact the range of the Lyme vector species, ticks, which will in turn expand the range of human risk. Although I could not successfully map the possible spread of tick populations or Lyme disease incidence as a result of climate change, my research shows a direct connection between infected tick geographic distribution and key climatic variables, such as temperature, humidity, and precipitation. It is expected that as the climate changes, particularly as it warms, the range of suitable habitat for ticks will expand into high latitudes and altitudes. The expansion of tick populations will put previously unaffected human populations at greater risk of Lyme disease. It is essential that further research be done to confirm the possible consequences of climate change on Lyme disease in the United States and to gain a more precise understanding of how and where effects will be seen. Health officials and policymakers must be informed so they can properly educate and prepare people preemptively for potential Lyme disease outbreaks.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 5 uppsatser.

Thesis (M.Sc. (Pharmacy))--Mahidol University, 1982.

Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.