Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

On Projective Plane of Order 13 with a Frobenius Group of Order 39 as a Collineation Group

One of the most outstanding problems in combinatorial mathematics and geometry is the problem of existence of finite projective planes whose order is not a prime power.

The Automorphism Group of the Free Algebra of Rank Two

The theorem of Czerniakiewicz and Makar-Limanov, that all the automorphisms of a free algebra of rank two are tame is proved here by showing that the group of these automorphisms is the free product of two groups (amalgamating their intersection), the group of all affine automorphisms and the group of all triangular automorphisms. The method consists in finding a bipolar structure. As a consequence every finite subgroup of automorphisms (in characteristic zero) is shown to be conjugate to a group of linear automorphisms.

New Symmetric (61,16,4) Designs Invariant Under the Dihedral Group of Order 10

∗ This work has been partially supported by the Bulgarian NSF under Contract No. I-506/1995.

Structure of the Unit Group of FD10

2000 Mathematics Subject Classification: 16U60, 20C05.

Cognitive-behavioural phenotype in a group of girls from 1.2 to 12 years old with the Incontinentia Pigmenti syndrome:recommendations for clinical management

Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive-behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Five girls had severe to mild intellectual deficiencies and the remaining nine had a normal neurodevelopment. Four girls were of school age and two of these showed no intellectual disability, but had specific disabilities in calculation and arithmetic reasoning. This is the first description of the cognitive-behavioural profile in relation to developmental age. We stress the importance of an early assessment of learning abilities in individuals with IP without intellectual deficiencies to prevent the onset of any such deficit.

A computer based approach to improve the dietary and physical activity patterns of a diverse group of adolescents

Diet and physical activity patterns have been implicated as major factors in the increasing prevalence of childhood and adolescent obesity. It is estimated that between 16 and 33 percent of children and adolescents in the United States are overweight (CDC, 2000). Moreover, the CDC estimates that less than 50% of adolescents are physically active on a regular basis (CDC, 2003). Interventions must be focused to modify these behaviors. Facilitating the understanding of proper nutrition and need for physical activity among adolescents is the first step in preventing overweight and obesity and delaying the development of chronic diseases later in life (Dwyer, 2000). The purpose of this study was to compare the outcomes of students receiving one of two forms of education (both emphasizing diet and physical activity), to determine whether a computer based intervention (CBI) program using an interactive, animated CD-ROM would elicit a greater behavior change in comparison to a traditional didactic intervention (TDI) program. A convenience sample of 254 high school students aged 14-19 participated in the 6-month program. A pre-test post-test design was used, with follow-up measures taken at three months post-intervention. ^ No change was noted in total fat, saturated fat, fruit/vegetables, or fiber intake for any of the groups. There was also no change in perceived self-efficacy or perceived social support. Results did, however, indicate an increase in nutrition knowledge for both intervention groups (p<0.001). In addition, the CBI group demonstrated more positive and sustained behavior changes throughout the course of the study. These changes included a decrease in BMI (ppre/post<0.001, ppost/follow-up<0.001), number of meals skipped (ppre/post<0.001), and soda consumption (ppre/post=0.003, ppost/follow-up=0.03) and an increase in nutrition knowledge (ppre/post<0.001, ppre/follow-up <0.001), physical activity (ppre/post<0.05, p pre/follow-up<0.01), frequency of label reading (ppre/follow-up <0.0l) and in dairy consumption (ppre/post=0.03). The TDI group did show positive gains in some areas post intervention, however a return to baseline behavior was shown at follow-up. Findings of this study suggest that compared to traditional didactic teaching, computer-based nutrition and health education has greater potential to elicit change in knowledge and behavior as well as promote maintenance of the behavior change over time. ^

The effect of osteoporosis education on calcium intake and physical activity in a group of community-dwelling Black older adults

The unprecedented increase in the number of older adults is expected to increase the burden of osteoporosis on the individual and society. Blacks have been understudied in osteoporosis prevention education research. Although the risk of osteoporosis is low in this population, its consequences are significant. This study employs a two-group experimental design (experimental and wait-list control groups) to evaluate the effect of an osteoporosis education on two osteoporosis prevention behaviors (OPBs)—calcium intake (CI) and physical activity (PA), in a group of community-dwelling Black older adults, 50 years and older resident in South Florida. A final sample of 110 (mean age 70.15 years), 90% female and 10% male completed a battery of questionnaires at two assessment periods. The experimental group participated in six weekly education program sessions immediately following baseline assessment, and the wait-list control group received the education following end of program assessment by all participants. The weekly educational sessions were conducted in social settings (church or senior center) employing constructs of the Revised Health Belief Model. The sessions focused on improving CI; osteoporosis knowledge (OKT), self-efficacy (SE), health beliefs (HB) and PA. Findings revealed significantly greater increase in reported CI ( M = 556 mg, Wilks’ λ = .47, F (1,108)=122.97, p< .001, η2=.53), OKT (p< .001), and SE (p< .001) among participants in the experimental compared to the wait-list control group. There was no significant difference between the two groups for PA and most of the HB subscales. OKT and SE were the best predictors of CI, while perceived barrier was a predominant factor predicting PA. Over the study period, a change in SE was the only variable related to changes in both OPBs. Attrition rate was lower than expected, which can be attributed to the settings utilized for the study. These findings support the importance of utilizing a familiar social setting. These results suggested the effectiveness of a program offered in multiple short sessions among this underserved minority population to improve OKT and SE resulting in a change in OPBs (increase in CI). However, there is need to explore alternative strategies to improve PA in this population group.

Developing a leadership identity: A case study exploring a select group of Hispanic women at a Hispanic serving institution

Leadership is a socially constructed concept shaped by the context, values and experiences of society (Klenke, 1996); the historical context of gender and ethnicity in society affects views about leadership and who merits a leadership role. Therefore, developing an understanding of Hispanic women students’ leadership identity development is critical in broadening how we define leadership and develop leadership education. The purpose of this qualitative case study was to explore and describe the leadership identity development of a select group of women leaders at a Hispanic Serving Institution (HSI) in the southeast. A psychosocial approach to the study was utilized. In-depth interviews and focus groups were conducted with 11 self-identified Hispanic women students of sophomore, junior or senior standing with varying degrees of involvement in leadership activities at Florida International University. Participants were asked questions related to four topics; (a) leadership, (b) gender, (c) ethnic identity, and (d) influences that contributed to their understanding of self as leader. Five topics emerged from the data presented by the participants’: (a) encouraging relationships, (b) meaningful experiences, (c) self development, (d) the role of gender, and (e) impact of ethnicity. These themes contributed to the leadership identity development of the participants. Findings indicate that leadership identity development for Hispanic women college students at this HSI is complex. The concept of leadership identity development presented in the literature was challenged as findings indicate that the participants’ experiences living and attending a school in a majority-minority city influenced their development of a leadership identity. The data indicate that leadership is not gender or ethnicity neutral as differences exist in expectations of men and women in leadership roles. Gender expectations posed particular challenges for these women student leaders. The prescriptive nature of stage-based models was problematic as findings indicated leadership identity development a complicated and continuing process influenced strongly by relationships and experiences. This study enhanced knowledge of the ways that Hispanic women students become leaders and the influences that shape their leadership experiences which can assist higher education professionals in developing leadership programs and courses that address gender, multiculturalism and awareness of self as leader.

The Effect of Osteoporosis Education on Calcium Intake and Physical Activity in a Group of Community-Dwelling Black Older Adults

The unprecedented increase in the number of older adults is expected to increase the burden of osteoporosis on the individual and society. Blacks have been understudied in osteoporosis prevention education research. Although the risk of osteoporosis is low in this population, its consequences are significant. This study employs a two-group experimental design (experimental and wait-list control groups) to evaluate the effect of an osteoporosis education on two osteoporosis prevention behaviors (OPBs) – calcium intake (CI) and physical activity (PA), in a group of community-dwelling Black older adults, 50 years and older resident in South Florida. A final sample of 110 (mean age 70.15 years), 90% female and 10% male completed a battery of questionnaires at two assessment periods. The experimental group participated in six weekly education program sessions immediately following baseline assessment, and the wait-list control group received the education following end of program assessment by all participants. The weekly educational sessions were conducted in social settings (church or senior center) employing constructs of the Revised Health Belief Model. The sessions focused on improving CI; osteoporosis knowledge (OKT), self-efficacy (SE), health beliefs (HB) and PA. Findings revealed significantly greater increase in reported CI (M = 556 mg, Wilks’ λ = .47, F(1,108)=122.97, p< .001, η2=.53), OKT (p< .001), and SE (p< .001) among participants in the experimental compared to the wait-list control group. There was no significant difference between the two groups for PA and most of the HB subscales. OKT and SE were the best predictors of CI, while perceived barrier was a predominant factor predicting PA. Over the study period, a change in SE was the only variable related to changes in both OPBs. Attrition rate was lower than expected, which can be attributed to the settings utilized for the study. These findings support the importance of utilizing a familiar social setting. These results suggested the effectiveness of a program offered in multiple short sessions among this underserved minority population to improve OKT and SE resulting in a change in OPBs (increase in CI). However, there is need to explore alternative strategies to improve PA in this population group.

Planning of schools as communities

The purpose of this research paper was to conduct a literature review to explore both the physical and historical aspects of schools and their communities in order to ascertain the nature of the disconnect that exists today between schools and communities. This paper reviews the purpose of the public school, from the origin of the one-room schoolhouse to today's urban schools; the impact of immigration, segregation, technology and industrialization on the public school and the forces behind public school reform. The reform processes and the programs developed to stimulate the public school including the transformation of the learning environment in the communities they serve was discussed. The research indicates that the return to a community school with small learning environments that involves communities and residents in the planning of schools as communities, is the most promising form of public school reform.

Molecular diversity, cultivation, and improved detection by fluorescent in situ hybridization of a dominant group of human gut bacteria related to Roseburia spp. or Eubacterium rectale

Peer reviewed

Molecular diversity, cultivation, and improved detection by fluorescent in situ hybridization of a dominant group of human gut bacteria related to Roseburia spp. or Eubacterium rectale

Peer reviewed

On the autonomous norm on the group of Hamiltonian diffeomorphisms of the torus

27 pages, 6 figures

Bernice E. Cullinan with a group of children reading around a table

Inscription: Verso: Bernice E. Cullinan, president, International Reading Association, surrounded by children reading magazines, New York.