Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1623. Adviser: Luisa Franzini. Includes bibliographical references (leaves 78-80).

Source: Masters Abstracts International, Volume: 47-06, page: 3544. Advisers: John R. Herbold; Sharon Cooper. Includes bibliographical references.

Ricin and Shiga toxin type 1 are potent cytotoxins known as ribosome inhibition proteins, abbreviated RIPs. Proteins of this family shut down protein synthesis by removing a critical adenine in the conserved stem-loop structure of 28S rRNA. Due to its exquisite cytotoxicity, the plant toxin ricin has been used as a biological warfare agent. Although great achievement has been made on ricin research, including catalytic mechanism and structure analysis, there is still no specific treatment available for ricin exposure. In addition, ricin A chain inhibitors may also be useful against the homologous bacterial proteins shiga toxins, which are responsible for dysentery, and diseases related to food poisoning, including hemolytic uremic syndrome. Previous study on RTA inhibitor search has provided a number of substrate analog inhibitors, all of which, however, are weaker inhibitors. Therefore, the goal of this work is to improve the binding affinity of known inhibitors and to discovery new scaffolds for inhibitor discovery and development. In this work, multiple approaches were employed for this purpose, including optimizing known inhibitors and searching new inhibitors by Virtual Drug Screening (VDS) and High Throughput Screening (HTS). A number of new RTA inhibitors were discovered by these strategies, which provide a variety of pharmacophores for RTA inhibitor design, and also added a new line of evidence for VDS as an advanced technology for drug discovery and development. / text

Malnutrition is a significant issue affecting the health of many adults over the age of 65. Screening for malnutrition in this population can help identify those in need of a complete nutritional assessment. Many screening tools have been developed to aid healthcare team members in identifying those at risk for malnutrition. A population of dietitians with a focus in older adult nutrition was surveyed to determine dietitians’ perceptions and use of screening tools for the older adult. The results of the study showed many dietitians did not use validated screening tools at their place of work and were not confident in their knowledge regarding the topic. Despite dietitians’ having the expertise in nutrition, other interdisciplinary team members are performing the screening in many settings in the United States and some dietitians’ feel this is an obstacle in identifying older adults at risk.

Background  Celiac disease (CD) is a chronic disorder in genetically predisposed individuals in which damage to the small intestine is caused by eating foods containing gluten. The prevalence has been shown to vary from around 1-3%, but most people with CD are undiagnosed. An option for finding those with unrecognized CD would include screening the general population, i.e., mass screening. However, screening identifies a pre-disease or disease condition in people who are presumed healthy and have not sought help. Therefore, the impacts of the screening process and being diagnosed through screening should be explored before such a public health intervention is considered. A population-based CD screening study involving 12-year-olds was undertaken in Sweden and provided an opportunity to explore these issues related to CD screening. Aims To make inferences about the potential impacts mass screening for CD can have on participants by exploring experiences and outcomes for participants involved in CD screening study. Methods and Subjects  Both qualitative (short written narratives) and quantitative (questionnaires with EQ-5D instrument) methods were used. Children who participated in the CD screening study were invited to write narratives at the time of the screening, before screening results were known, describing their experience with the screening (n=240). The EQ-5D instrument was used to measure and compare health-related quality of life reported by participants at the time of the screening and one year after the screening-detected participants received their diagnosis (screening-detected n=103, referents n=483). Those with screening-detected CD were also invited to write narratives one and five years after their diagnosis. In these narratives the adolescents described how it felt to be diagnosed with CD, how it felt to live with CD, and if they thought all children should be screened (one-year follow-up n=91, five-year follow-up n=72). Results  Even though some children experienced fear and anxiety during the screening, overall they had, or were provided with, tools that allowed them to cope well with the screening. The health-related quality of life reported by those with screening-detected CD was similar before and one year after diagnosis (and similar to that of the referents). We also found that after five years of living with the diagnosis there had been maintenance and evolution in the beliefs and practices of these adolescents. Being detected through screening and the threat of complications impacted how they felt about the diagnosis, coped with the gluten-free diet, and what they thought about CD screening. Five years after the screening-detected diagnosis the adolescents have adjusted to the disease and adapted new habits and coping strategies to deal with the gluten-free diet. However, there are still those who doubt the accuracy and benefit of the diagnosis.   Conclusions  Our findings suggest that it is possible for participants to avoid excess anxiety during CD screening. However, there was not consensus among participants that being detected and treated had improved their health-related quality of life or that the immediate benefits outweighed the harm caused by being detected in this way. When considering mass screening, the affect on the participants is important to take into account and our findings shed light on some of the potential impacts a CD mass screening could have on participants.

Cervical cancer is the second most common cancer, with about 500 000 new cases per year among women worldwide. With a well-organized screening programme the number of cases can be reduced by more than 50%. In spite of having such a screening programme there are still around 450 new cases yearly in Sweden. The majority of these cases occur in non-attendees. There is thus a need to improve the Swedish cervical cancer screening programme in order to further reduce the number of cases of cervical cancer. Cervical cancer and high-grade cervical dysplasia are caused by sexually transferred high-risk human papillomaviruses (HR-HPVs). In cases of persistent HR-HPV infection there is a risk of development of dysplasia and in some cases subsequent progress to cervical cancer. HR-HPV testing shows high sensitivity as regards the detection of cervical dysplasia. Self-sampling of vaginal fluid for the analysis of HR-HPV has many advantages, since a woman can perform the sampling herself in a private setting, whenever suitable, without the need to travel to a clinic. Our studies have shown that sensitivity in the detection of precancerous lesions is about twice as great with the HR-HPV self-test compared with cytology-based tests.  If a woman was HR-HPV-positive in two consecutive tests, the specificity of the HR-HPV test increased to about 98%. Among women with short-term persistent HR-HPV infection, the prevalence of CIN 2+ was over 40%. There was good concordance in sensitivity as regards the detection of CIN 2+ between self-obtained and physician-obtained samples, although self-sampling was associated with slightly lower specificity. The prevalence of HR-HPV from day to day in premenopausal women was not influenced by hormonal changes during the menstrual cycle. Neither were there significant day-to-day changes in postmenopausal women. A single self-test thus provides reliable information on whether or not a woman has an HR-HPV infection. In conclusion, self-sampling combined with the analysis of HR-HPV appears to be a powerful alternative as a primary screening method for the prevention of cervical cancer. Self-sampling for HR-HPV testing is a suitable, safe and accepted strategy for cervical cancer prevention among women.

This thesis focuses on the modelling and prediction of factors affecting attendance to screening invitations of the NHS Breast Screening Programme. The analysis is based on data collected by the Warwickshire, Solihull and Coventry Breast Screening Unit from 1989 up to 2001 with respect to invitation to screening for the prevention of breast cancer in non-symptomatic women. Using a novel approach to the analysis of the data, from the perspective of the screening episode of each woman, rather than the usual analysis from the perspective of the screening round of the units, a statistical analysis is carried out on the whole registered population for the first time. Amendments to the current formulae for coverage calculations, the introduction of a new parameter (invitation rate) and the proposal for a reduction of the invitation period (period of time between two consecutive invitations) follows from the analysis. A preliminary analysis of predictive methodologies, including traditional statistical methods and artificial intelligent methods, gives the foundation to the formulation of two new algorithms; the first, for the prediction of attendance of women to screening invitations, and the second for the prediction of occurrence of screening variation (change of appointment dates) of women to invitations. Both algorithms are based on neural network generated models able to learn from the previous screening behaviour history of the woman, a technique not previously explored for the prediction of attendance. The accuracy of the new proposed algorithm for the prediction of attendance to invitation is tested on a blind study using data not previously seen by the predictive system, and for which results were unknown at the time when the predictions were made. From the obtained results, it is concluded to recommend the implementation by the NHS Breast Screening Unit of the two algorithms proposed for the prediction of the women’s attendance and screening variation to their invitation for screening. With these predictions, women likely not to attend, or change appointment date, can be identified and appropriately targeted with the aim of increasing their attendance in the short term, and in the long term, reducing breast cancer mortality.

Dysfagi, sväljningssvårigheter, är en vanlig komplikation vid Alzheimers sjukdom och är väl utforskat i det sista av de tre stadierna vid demens (lindrig, måttlig och svår). Sväljningssvårigheter som har kopplats samman med Alzheimers sjukdom är ett förändrat ätbeteende, reducerad höjning av larynx och en längre oral fas. Syftet med studien var att undersöka om och vilka symtom vid dysfagi som kan ses i de tidigare stadierna av Alzheimers sjukdom vid användning av icke-invasiva undersökningsmetoder. En enkätundersökning med 16 deltagare och en sväljningsscreening med fyra deltagare genomfördes. Sväljningsscreeningen bestod av fyra delar: oralmotorik, sväljningstest och sväljningskapacitetstest med vatten och tuggfunktion. Resultaten från enkäten visade ingen högre andel med sväljningssvårigheter i den testade gruppen jämfört med tidigare forskning av normalpopulationen. Inga signifikanta samband mellan olika parametrar såsom poäng på Mini Mental Test (MMT), tid för diagnos och poäng på enkäten hittades. Resultaten från sväljningsscreeningen visade en tendens till förlängd orofaryngeal fas vid ett sväljningskapacitetstest vilket indikerar att undersökning av sväljningskapacitet kan vara en användbar metod för att identifiera tidiga sväljningssvårigheter vid Alzheimers sjukdom. Testet är lätt att genomföra och inte tidskrävande. / Dysphagia, eating disorders, is a common complication associated with Alzheimer’s disease and has been studied extensively in the three late stages of dementia (mild, moderate and severe). Eating disorders that have been linked to Alzheimer’s disease are a changed eating behaviour, reduced laryngeal elevation and a prolonged oral phase. The purpose of this study was to investigate if and which symptoms of dysphagia can be identified using non-invasive methods. A survey with 16 participants and a swallowing screening with four participants were conducted. The swallowing screening consisted of four parts: oral motor abilities, a swallowing test and a swallowing capacity test with water and chewing function. The results from the survey did not show an increased prevalence of eating disorders in the test group compared to what previous research suggests could be expected for the normal population. No significant correlations between parameters such as Mini Mental Test (MMT), time elapsed since diagnosis or score of the survey were found. The results from the swallowing screening showed a tendency towards a prolonged oropharyngeal phase in a swallowing capacity test, indicating that examination of swallowing capacity could be a useful method for identifying early eating disorders in Alzheimers disease. The test is easy to perform and is not time consuming.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 6 uppsatser.

Thesis (M.Ph.)--Georgia State University, 2007. / Title from file title page. Russ Toal, committee chair; Rebecca Cowens-Alvarado, Ike Okosun, committee members. Electronic text (119 p. : col. maps) : digital, PDF file. Description based on contents viewed June 4, 2008. Includes bibliographical references (p. 90-96).