Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

Evaluation of a date rape prevention program for new students in a university setting

The purpose of this study was to design, implement and evaluate the effectiveness of a date rape prevention program among new students at Rice University. Six-hundred and fifteen new students were randomly assigned to one of eight residential colleges or dormitories. The distribution of students to each of the dormitories was carried out in accordance with a stratified random sampling procedure. The study population was divided into strata based on ethnicity, gender, geographical region, and academic major. The number of students randomly assigned to each of the eight dormitories was approximately 75. After this procedure was completed, each of the colleges was randomly selected to either the intervention or control group. A randomized pretest and posttest control group design was used to assess changes in attitudes, self-efficacy, and behavior with regard to date rape. All participants were given an anonymous pretest and posttest measuring attitudes, self-efficacy, and behavior immediately prior to and following the intervention. The intervention group attended the play Scruples, designed to promote date rape prevention, after which they were immediately posttested. After this initial posttest the intervention group also participated in an interactive group role-playing activity led by trained peer instructors. The control group was pretested and subject to the placebo intervention of a multiculturalism play and was posttested immediately afterwards. Later in the week this group saw the Scruples play only. Both control and intervention groups were sent a two month follow-up survey questionnaire, to measure any changes in attitudes, self-efficacy, and behavior over time. As hypothesized students who saw the play Scruples showed a change in attitudes immediately posttest but no difference in self-efficacy or behavior. The two month follow-up survey showed no change in attitudes, self-efficacy, or behavior. There was a difference at pretest in males and females attitudes, with males showing significantly more rape tolerant attitudes than females. Thus, the proposed research findings will provide a better understanding of the attitudes that perpetuate date rape, and will inform strategies for prevention programs. ^

Collagen I modulates growth and gene expression in prostate cancer cells

Prostate cancer is the second leading cause of male cancer-related deaths in the United States. Interestingly, prostate cancer preferentially metastasizes to skeletal tissue. Once in the bone microenvironment, advanced prostate cancer becomes highly resistant to therapeutic modalities. Several factors, such as extracellular matrix (ECM) components, have been implicated in the spread and propagation of prostatic carcinoma. In these studies, we have utilized the PC3 cell line, derived from a human bone metastasis, to investigate the influence of the predominant bone ECM protein, type I collagen, on prostate cancer cell proliferation and gene expression. We have also initiated the design and production of ribozymes to specific gene targets that may influence prostate cancer bone metastasis. ^ Our results demonstrate that PC3 cells rapidly adhere and spread on collagen I to a greater degree than on fibronectin (FN) or poly-L-lysine (PLL). Flow cytometry analysis reveals the presence of the α1, α2 and α3 collagen binding integrin subunits. The use of antibody function blocking studies reveals that PC3 cells can utilize α2β 1 and α3β1 integrins to adhere to collagen I. Once plated on collagen I, the cells exhibit increased rates of proliferation compared with cells plated on FN or tissue culture plastic. Additionally, cells plated on collagen I show increased expression of proteins associated with progression through G1 phase of the cell cycle. Inhibitor studies point to a role for phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and p70 S6 kinase in collagen I-mediated PC3 cell proliferation and cyclin D1 expression. To further characterize the effect of type I collagen on prostate cancer bone metastasis, we utilized a cDNA microarray strategy to monitor type I collagen-mediated changes in gene expression. Results of this analysis revealed a gene expression profile reflecting the increased proliferation occurring on type I collagen. Microarray analysis also revealed differences in the expression of specific gene targets that may impact on prostate cancer metastasis to bone. ^ As a result of our studies on the interaction of prostate cancer cells and the skeletal ECM, we sought to develop novel molecular tools for future gene therapy of functional knockdown experiments. To this end, we developed a series of ribozymes directed against the α2 integrin and at osteopontin, a protein implicated in the metastasis of various cancers, including prostate. These ribozymes should facilitate the future study of the mechanism of prostate cancer cell proliferation, and disease progression occurring at sites of skeletal metastasis where a type I collagen-based environment predominates. ^ Together these studies demonstrate the involvement of bone ECM proteins on prostate cancer cell proliferation and suggest that they may play a significant role on the growth of prostate metastases once in the bone microenvironment. ^

Design and implementation of a clinical dashboard

In a large health care system, the importance of accurate information as feedback mechanisms about its performance is necessary on many levels from the senior level management to service level managers for valid decision-making purposes. The implementation of dashboards is one way to remedy the problem of data overload by providing up-to-date, accurate, and concise information. As this health care system seeks to have an organized, systematic review mechanism in place, dashboards are being created in a variety of the hospital service departments to monitor performance indicators. The Infection Control Administration of this health care system is one that does not currently utilize a dashboard but seeks to implement one. ^ The purpose of this project is to research and design a clinical dashboard for the Infection Control Administration. The intent is that the implementation and usefulness of the clinical dashboard translates into improvement in the measurement of health care quality.^

The impact of communication and cultural diversity in utilizing dental services among Saudi Arabian students in U.S.A.

Objectives: The purpose of this study is to understand the perceived effects of patient-dental staff communication and cultural diversity on the utilization of dental services in the U.S. by Saudi Arabian students who live in the U.S. and enrolled into the King Abdullah Scholarship program. Methods: The study design was an analytical cross-sectional study. Data for this study was obtained from the Saudi Dental Servicers Utilization Survey, a voluntary internet survey available online for one month through Facebook. Ordered logistic regression analyses and multinomial logistic regression analyses were used to measure the relationships between patient-dental staff communication and cultural diversity on the utilization of dental services. Results: Eight hundred and forty-seven responses were analyzed for this study. Overall, the majority of Saudi students reported having excellent communication experience with dental providers in the U.S. More than 58% of respondents reported at least one regular dental visit last year. Factors that influenced the use of regular dental care were: dentist's explanation of treatment plan, response of dental staff to patient's needs, respectful and polite dental staff, dental staff kindness, availability of up-to-date equipment, and overall communication with dentist. However, the utilization of emergency dental care was not associated with any measurement of patient-dental provider communication. Overall future utilization of dental care is associated with all aspects of patient-dental staff communication measured in this survey. Furthermore, more utilization of regular dental care was related to respondent's perception of the importance of trustworthiness dental staff and the importance of a dentist's reputation was only marginally associated. Respondent's perception of dentist's reputation was associated with more use of emergency dental services. Respondents are more likely to anticipate using dental care in the future if they perceived trustworthiness dental staff, and the dentist's reputation as influencing factors to their usage of dental services. Conclusions: Patient-dental staff communication was partially associated with utilization of regular dental care, not associated with utilization of emergency dental care, and broadly associated with anticipated future utilization of dental care. In addition, trustworthy dental staff, and a dentist's reputation were considered to be strong influencing factors towards utilization of dental services.^