The Role of Serum Amyloid P in Amyloidosis

Amyloid is a term used to describe a set of diseases caused by protein misfolding. There are 36 proteins known to undergo amyloidosis to date. They each unfold from their unique native states and refold into a specific cross β- sheet motif to which various macromolecules can bind. These protein deposits invade tissues and organs disrupting tissue structure and function. The protein serum amyloid P (SAP) is a universal component to all amyloid deposits regardless of the protein involved. It is a disc shaped protein which is known to protect amyloid fibres against degradation. The role of SAP in amyloidosis has been a subject of discussion for many years. Some have found SAP to enhance fibre formation whereas others have found SAP to prevent it. This thesis can be divided into two parts. The first half focuses on the molecular analysis of SAP in relation to amyloid fibre growth whereas the second half focuses solely on the structural aspects of SAP. Chapters 2 and 3 demonstrate that SAP actually exhibits a dual role in relation to fibrillogenesis. It is capable of acting as both a chaperone and a fibrillogenic enhancer depending on its conformation at the time. As a monomer SAP is responsible for the enhancement and stabilisation of fibres whereas in its dimerised form it demonstrates characteristics similar to that of a molecular chaperone. Recent developments in amyloid treatment involve the removal of SAP from deposits using anti-SAP antibodies. As of yet, structural analysis has not been carried out on the SAP:antibody complex. Chapters 4 and 5 conclude this thesis by using crystallographic techniques to demonstrate that a single antibody binds to an SAP molecule during dissociation from amyloid deposits

Solid Waste Management in a Leprosarium in Southwestern Nigeria

Waste from healthcare institutions generally ought to be treated and disposed hygienically. However, the type of institution normally determines the material component and the nature of the waste generated whether it is hazardous or non-hazardous, infectious or non-infectious waste. Also health status of an individual or community is a function of standard of living, medical services available, social amenities and hygienic environment normally determined through impact assessment. These have been examined in relation to the leprosarium in Ogbomosho, Southwestern Nigeria. The leprosarium under study consists of a clinic and three camps located at about 1000m from the clinic. The leprosarium housed 30 patients, while the camps served as home for about 140 people under rehabilitation together including their children. As one of the health institutions, it is apparent that the waste generated is heterogeneous mixture of both general municipal waste and bio-medical waste. The percentage of biomedical waste which is hazardous in nature is low about 1.0% with average generation rate of 0.13kg/day while that of non-hazardous, non-infectious general waste is 0.288kg/person/day. The average waste generation rate in term of mass is determined to be between 0.084 – 0.095kg/person/day which reveals the poor status and rural nature of these leper settlements. The waste components consist of bandages and swabs, paper, nylon and plastic, domestic waste, animal waste (mostly goat manure), wood ash and yard trimmings which are being disposed on open dump sites and sometimes by open burning which are unhygienic causing health hazards. Accumulation of these waste components without proper disposal initiates its putrefaction which produces offensive odour. In addition, absence of adequate sanitary facilities has promoted open defecation which is a source of infectious, diseases. As an economical, appropriate and useful method of waste disposal, composting was proposed since it is found relevant and acceptable  for the leprosarium and the settlements around as the waste generated is predominantly biodegradable and decomposable materials. Key words: Solid waste, bio-medical waste, characterization, waste disposal, compostin

Cervical Screening and General Physical Examination Behaviors of Women Exposed In Utero to Diethylstilbestrol

Objective. To estimate whether women exposed in utero to diethylstilbestrol (DES) report receiving more cervical and general physical examinations compared to unexposed women. Materials and Methods. 1994 Diethylstilbestrol Adenosis cohort data are used to assess the degree of recommended compliance of cervical screenings found in 3,140 DES-exposed and 826 unexposed women. Participants were enrolled at 4 sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data, which included reported frequency over the preceding 5 years (1990-1994) of Papanicolaou smears and general physical examinations. Results. Diethylstilbestrol-exposed women exceeded the recommended frequency of Papanicolaou smear screenings [adjusted odds ratio (aOR) = 2.15, 95% CI (confidence interval) = 1.60-2.88] compared to the unexposed. This association held among those without a history of cervical intraepithelial neoplasia (aOR = 1.88, 95% CI = 1.35-2.62). Diethylstilbestrol-exposed women exceeded annual recommendations for physical examinations (aOR = 2.27, 95% CI = 1.16-4.43) among women without a history of chronic disease when compared to unexposed women. Conclusions. Most DES-exposed women are receiving cervical cancer screening at least at recommended intervals, but one third of the women are not receiving annual Papanicolaou smear examinations

Life-course blood pressure in relation to brain volumes

The impact of blood pressure on brain volumes may be time- or pattern-dependent

Migraine and white matter hyperintensities: The ARIC MRI study

OBJECTIVE: Migraine is associated with white matter hyperintensities (WMH) cross-sectionally, but its effect on WMH progression is uncertain. METHODS: Participants in the Atherosclerosis Risk in Communities cohort study (n = 10,924) completed a standardized headache questionnaire between 1993 and 1995. A subset of participants (n = 1,028) received 2 MRIs 8 to 12 years apart: once at the time of headache ascertainment, and again from 2004 to 2006. WMH were quantified using both a visually graded score (0-9) and semiautomated volumetric analysis. Linear and logistic regression models adjusted for age, sex, and other vascular risk factors were constructed. RESULTS: Individuals who had migraine without aura were cross-sectionally associated with an 87% greater odds of having a WMH score ≥3 than individuals without headache (adjusted odds ratio = 1.87; 95% confidence interval [CI]: 1.04, 3.37). Participants with migraine had an average of 2.65 cm(3) more WMH than those without headache (95% CI: 0.06, 5.24). However, there was no significant difference in WMH progression over the study period between individuals with and without migraine (1.58 cm(3) more progression for individuals with migraine compared to those without; 95% CI: -0.37, 3.53). CONCLUSION: Migraine is associated with WMH volume cross-sectionally but not with WMH progression over time. This suggests that the association between migraine and WMH is stable in older age and may be primarily attributable to changes occurring earlier in life, although further work is needed to confirm these findings

Life-course blood pressure in relation to brain volumes

The impact of blood pressure on brain volumes may be time- or pattern-dependent

Global Genetic Population Structure of Bacillus anthracis

Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical and current importance that is found throughout the world. The basis of its historical transmission is anecdotal and its true global population structure has remained largely cryptic. Seven diverse B. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by phylogenetic reconstruction of these characters onto an evolutionary model. This analysis identified SNPs that define the major clonal lineages within the species. These SNPs, in concert with 15 variable number tandem repeat (VNTR) markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42 countries to create an extensive genotype data set. These analyses subdivided the isolates into three previously recognized major lineages (A, B, and C), with further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221 unique MLVA15 genotypes. This rare genomic variation was used to document the evolutionary progression of B. anthracis and to establish global patterns of diversity. Isolates in the A lineage are widely dispersed globally, whereas the B and C lineages occur on more restricted spatial scales. Molecular clock models based upon genome-wide synonymous substitutions indicate there was a massive radiation of the A lineage that occurred in the mid-Holocene (3,064–6,127 ybp). On more recent temporal scales, the global population structure of B. anthracis reflects colonial-era importation of specific genotypes from the Old World into the New World, as well as the repeated industrial importation of diverse genotypes into developed countries via spore-contaminated animal products. These findings indicate humans have played an important role in the evolution of anthrax by increasing the proliferation and dispersal of this now global disease. Finally, the value of global genotypic analysis for investigating bioterrorist-mediated outbreaks of anthrax is demonstrated

The role of organic nutrients in structuring freshwater phytoplankton communities in a rapidly changing world

Carbon, nitrogen, and phosphorus are critical macroelements in freshwater systems. Historically, researchers and managers have focused on inorganic forms, based on the premise that the organic pool was not available for direct uptake by phytoplankton. We now know that phytoplankton can tap the organic nutrient pool through a number of mechanisms including direct uptake, enzymatic hydrolysis, mixotrophy, and through symbiotic relationships with microbial communities. In this review, we explore these mechanisms considering current and projected future anthropogenically-driven changes to freshwater systems. In particular, we focus on how naturally- and anthropogenically- derived organic nutrients can influence phytoplankton community structure. We also synthesize knowledge gaps regarding phytoplankton physiology and the potential challenges of nutrient management in an organically dynamic and anthropogenically modified world. Our review provides a basis for exploring these topics and suggests several avenues for future work on the relation between organic nutrients and eutrophication and their ecological implications in freshwater systems