Determining the Role of Casz1 in Heart Development

Castor (Casz1) is a zinc finger transcription factor that has been shown to be required for heart development in Xenopus. Casz1 has also been linked to high blood pressure and hypertension in humans through a recent Genome Wide Association Study. The purpose of this research was to determine the role of Casz1 in cardiac development and how Casz1 fits into the cardiac transcription program. A mouse model was used because of the high genomic conservation between mice and humans. To determine the spatial and temporal expression of Casz1 mRNA during murine heart development, I utilized in situ hybridization. In addition, to confirm that CASZ1 protein is present in the developing heart, I performed immunohistochemistry. My studies showed that Casz1 is expressed in the atria and left ventricle of the developing heart. To determine the role of Casz1 in cardiac development, I examined the cardiomyocyte mitotic index of wild type embryos and Casz1 mutant embryos, and demonstrated that cardiomyocytes lacking Casz1 over-proliferate. This indicates that Casz1 regulates cardiomyocyte proliferation. Future studies are aimed at identifying genes that Casz1 regulates, providing further insight into the cardiac gene program. These studies hold implications for understanding congenital heart defects by giving us further insight into the molecular mechanisms that regulate cardiac development.Bachelor of Scienc

The segue from city to stage : facades, marquees, entries, lobbies in New York theater

Thesis (M.Arch)--Massachusetts Institute of Technology, Dept. of Architecture, 1984.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH.Bibliography: leaves 155-158.by Caroline Stacy Labiner.M.Arc

Social and family characteristics of Hispanics with epilepsy

AbstractThe purpose of this study is to determine how acculturation, social support, family emotional involvement, perceived family criticism and stigma are associated with epilepsy self-efficacy and depression. A principal components analysis (PCA) was used to describe the salience of these characteristics within a sample of Hispanics with epilepsy.A total of 50 Hispanic adults of Mexican descent identified in our Epilepsy Clinic participated in this study. The PCA identified four distinct types, two were relatively culture-free, and two were distinctly culturally oriented. The first non-culture affiliated type described a well-adjusted group of individuals that tended to be males with moderate self-efficacy, who received social support, and who were unlikely to have depression or feel stigmatized. The second non-culture affiliated type described a dimension in which family emotional involvement tended to co-occur with perceived criticism. The Anglo-oriented group had a family environment that did not appear to criticize the individual with epilepsy and had good self-efficacy. The Mexican-oriented group had high self-efficacy and was unlikely to have depression. Results suggest that acculturation variables must be taken into consideration among ethnic groups because social, psychological and acculturation variables interact in complex ways. Additionally, it is clear that a diagnosis of epilepsy does not automatically lead to poor quality of life, stigma, or depression

Activity-dependent heteromerization of the hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels: role of N-linked glycosylation.

Formation of heteromeric complexes of ion channels via co-assembly of different subunit isoforms provides an important mechanism for enhanced channel diversity. We have previously demonstrated co-association of the hyperpolarization activated cyclic-nucleotide gated (HCN1/HCN2) channel isoforms that was regulated by network (seizure) activity in developing hippocampus. However, the mechanisms that underlie this augmented expression of heteromeric complexes have remained unknown. Glycosylation of the HCN channels has been implicated in the stabilization and membrane expression of heteromeric HCN1/HCN2 constructs in heterologous systems. Therefore, we used in vivo and in vitro systems to test the hypothesis that activity modifies HCN1/HCN2 heteromerization in neurons by modulating the glycosylation state of the channel molecules. Seizure-like activity (SA) increased HCN1/HCN2 heteromerization in hippocampus in vivo as well as in hippocampal organotypic slice cultures. This activity increased the abundance of glycosylated HCN1 but not HCN2-channel molecules. In addition, glycosylated HCN1 channels were preferentially co-immunoprecipitated with the HCN2 isoforms. Provoking SA in vitro in the presence of the N-linked glycosylation blocker tunicamycin abrogated the activity-dependent increase of HCN1/HCN2 heteromerization. Thus, hippocampal HCN1 molecules have a significantly higher probability of being glycosylated after SA, and this might promote a stable heteromerization with HCN2

Experiences of Using the Mindset Self-Management Mobile Health App Among Hispanic Patients: Results of a Qualitative Study

BACKGROUND: Interventions focusing on epilepsy self-management (ESM) are vital for promoting the health of people living with epilepsy. E-technology and mobile health (mHealth) tools are becoming increasingly integrated into practice to promote self-management strategies for chronic diseases, enhance care delivery, and reduce health disparities. Management Information and Decision Support Epilepsy Tool (MINDSET), a bilingual decision support tool (available in English and Spanish), was found to be both feasible and effective in facilitating goal-based ESM in the clinic. PURPOSE: To assess the experience of using MINDSET as an ESM intervention among Hispanic patients with epilepsy to inform future interventional studies. METHODS: This study used a Qualitative Descriptive (QD) framework to provide a rich and straightforward description of patients\u27 subjective experiences using MINDSET. Participants were enrolled in the intervention group of a larger parent study (RCT) to assess the efficacy of MINDSET among Hispanic People with Epilepsy (PWE). The purposive, convenient, criterion-based sample for this qualitative analysis comprised of 42 patients who agreed to participate in a semi-structured interview at the end of the larger RCT. This RCT was conducted between August 2017 and January 2019. Spanish and English-speaking Hispanic adult patients (n = 94) with epilepsy in Arizona (n = 53) and Texas (n = 41) were randomly assigned within 6 neurology clinics to treatment (MINDSET plus Usual Care, hereafter referred to as MINDSET; n = 46) and comparison (Usual Care Only; n = 48) conditions. RESULTS: Patient demographics, epilepsy conditions, and ESM behavioral characteristics were representative of the intervention group. Study participants were Hispanic, mainly of Mexican descent (94 %), with a mean age of 39 years, mostly female (53 %), and most of the participants reported having had one or more seizures per month (54 %). The MINDSET intervention revealed five ESM themes: (1) Awareness and Realization of Epilepsy Self-Management, (2) Communication and Partnership with Health Care Providers HCP, (3) Epilepsy Self-Management and Quality of Life, (4) Seizure Control, and (5) Optimism and Agency. CONCLUSION: The participants who used MINDSET as a self-management intervention reported an overall positive experience. Qualitative data in this study show that MINDSET is a valuable ESM tool for Hispanic patients with epilepsy. Findings from this qualitative study were consistent with results from a larger parent study that recognized MINDSET as an effective platform for improving epilepsy self-management adherence

The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia.

OBJECTIVE: Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. METHODS: We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. RESULTS: Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis (MTS) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] -27.3% to -67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography (EEG) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. SIGNIFICANCE: These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well-established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed

Awareness and Prevalence of Human Milk Sharing and Selling in the United States

There are limited data available about the prevalence of human milk (HM) sharing and selling in the general population. We aimed to describe attitudes toward HM selling among participants in a qualitative‐interview study and prevalence of HM sharing and selling among a national sample of U.S. mothers. Mothers (n = 41) in our qualitative‐interview study felt that sharing or donating HM was more common than selling; none had ever purchased or sold HM. Three themes related to HM selling emerged from this work: questioning the motives of those selling HM, HM selling limits access to HM to those with money, and HM selling is a legitimate way to make money. Some mothers had reservations about treating HM as a commodity and the intentions of those who profit from the sale of HM. Nearly all participants in our national survey of U.S. mothers (94%, n = 429) had heard of infants consuming another mother\u27s HM. Approximately 12% had provided their milk to another; half provided it to someone they knew. Fewer mothers (6.8%) reported that their infant had consumed another mother\u27s HM; most received this HM from someone they knew. A smaller proportion of respondents (1.3%) had ever purchased or sold HM. Among a national sample of U.S. mothers, purchasing and selling HM was less common than freely sharing HM. Together, these data highlight that HM sharing is not uncommon in the United States. Research is required to create guidelines for families considering HM sharing

Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian cardiac development

Organ growth occurs through the integration of external growth signals during the G1 phase of the cell cycle to initiate DNA replication. Although numerous growth factor signals have been shown to be required for the proliferation of cardiomyocytes, genetic studies have only identified a very limited number of transcription factors that act to regulate the entry of cardiomyocytes into S phase. Here, we report that the cardiac para-zinc-finger protein CASZ1 is expressed in murine cardiomyocytes. Genetic fate mapping with an inducible Casz1 allele demonstrates that CASZ1-expressing cells give rise to cardiomyocytes in the first and second heart fields. We show through the generation of a cardiac conditional null mutation that Casz1 is essential for the proliferation of cardiomyocytes in both heart fields and that loss of Casz1 leads to a decrease in cardiomyocyte cell number. We further report that the loss of Casz1 leads to a prolonged or arrested S phase, a decrease in DNA synthesis, an increase in phospho-RB and a concomitant decrease in the cardiac mitotic index. Taken together, these studies establish a role for CASZ1 in mammalian cardiomyocyte cell cycle progression in both the first and second heart fields

A survey on knowledge and self-reported formula handling practices of parents and child care workers in Palermo, Italy

Powdered infant formula (PIF) is not a sterile product, but this information appears to be poorly diffused among child caregivers. Parents and child care workers may behave in an unsafe manner when handling PIF. Methods: This study involved parents and child care workers in the 24 municipal child care centres of Palermo. Knowledge and self-reported practices about PIF handling were investigated by a structured questionnaire. A Likert scale was used to measure the strength of the respondent's feelings. Association of knowledge and self-reported practices with demographic variables was also evaluated. Results: 42.4% of parents and 71.0% of child care workers filled in the questionnaire. Significant differences were found between parents and child care workers for age and education. 73.2% of parents and 84.4% of child care workers were confident in sterility of PIF. Generally, adherence to safe procedures when reconstituting and handling PIF was more frequently reported by child care workers who, according to the existing legislation, are regularly subjected to a periodic training on food safety principles and practices. Age and education significantly influenced the answers to the questionnaire of both parents and child care workers. Conclusion: The results of the study reveal that parents and child care workers are generally unaware that powdered formulas may contain viable microorganisms. However, child care workers consistently chose safer options than parents when answering the questions about adherence to hygienic practices. At present it seems unfeasible to produce sterile PIF, but the risk of growth of hazardous organisms in formula at the time of administration should be minimized by promoting safer behaviours among caregivers to infants in both institutional settings and home. \ua9 2009 Calamusa et al; licensee BioMed Central Ltd