Comparative studies of Hox genes in mammalian limb and vertebral pattern formation

Divergence of anterior-posterior (AP) limb pattern and differences in vertebral column morphology are the two main examples of mammalian evolution. The Hox genes (homeobox containing gene) have been implicated in driving evolution of these structures. However, regarding Hox genes, how they contribute to the generation of mammalian morphological diversities, is still unclear. Implementing comparative gene expression and phenotypic rescue studies for different mammalian Hox genes could aid in unraveling this mystery. In the first part of this thesis, the expression pattern of Hoxd13 gene, a key Hox gene in the establishment of the limb AP pattern, was examined in developing limbs of bats and mice. Bat forelimbs exhibit a pronounced asymmetric AP pattern and offer a good model to study the molecular mechanisms that contribute to the variety of mammalian limbs. The data showed that the expression domain of bat Hoxd13 was shifted prior to the asymmetric limb plate expansion, whereas its domain in mice was much more symmetric. This finding reveals a correlation between the divergence of Hoxd13 expression and the AP patterning difference in limb development. The second part of this thesis details a phenotypic rescue approach by human HOXB1-9 transgenes in mice with Hoxb1-9 deletion, The mouse mutants displayed homeosis in cervical and anterior thoracic vertebrae. The human transgenes entirely rescued the mouse mutants, suggesting that these human HOX genes have similar functions to their mouse orthologues in anterior axial skeletal patterning. The anterior expressing human HOXB transgenes such as HOXB1-3 were expressed in the mouse embryonic trunk in a similar manner as their murine orthologues. However, the anterior boundary of human HOXB9 expression domain was more posterior than that of the mouse Hoxb9 by 2-3 somites. These data provide the molecular support for the hypothesis that Hox genes are responsible for maintaining similar anterior axial skeletal architectures cervical and anterior thoracic regions, but different architectures in lumbar and posterior thoracic regions between humans and mice. ^

The detrimental role of angiotensin receptor agonistic autoantibodies in intrauterine growth restriction seen in preeclampsia.

Growth-restricted fetuses are at risk for a variety of lifelong medical conditions. Preeclampsia, a life-threatening hypertensive disorder of pregnancy, is associated with fetuses who suffer from intrauterine growth restriction (IUGR). Recently, emerging evidence indicates that preeclamptic women harbor AT(1) receptor agonistic autoantibodies (AT(1)-AAs) that contribute to the disease features. However, the exact role of AT(1)-AAs in IUGR and the underlying mechanisms have not been identified. We report that these autoantibodies are present in the cord blood of women with preeclampsia and retain the ability to activate AT(1) receptors. Using an autoantibody-induced animal model of preeclampsia, we show that AT(1)-AAs cross the mouse placenta, enter fetal circulation, and lead to small fetuses with organ growth retardation. AT(1)-AAs also induce apoptosis in the placentas of pregnant mice, human villous explants, and human trophoblast cells. Finally, autoantibody-induced IUGR and placental apoptosis are diminished by either losartan or an autoantibody-neutralizing peptide. Thus, these studies identify AT(1)-AA as a novel causative factor of preeclampsia-associated IUGR and offer two possible underlying mechanisms: a direct detrimental effect on fetal development by crossing the placenta and entering fetal circulation, and indirectly through AT(1)-AA-induced placental damage. Our findings highlight AT(1)-AAs as important therapeutic targets.

Qualitative study: Understanding Mexican American women's experience in intimate partner violence

The purpose of this qualitative study was to gain an understanding of the experiences of Mexican American women living with intimate partner abuse relevant to the process of disclosure of abuse. Limited research exists on the experiences of women who are of Mexican descent living with intimate partner abuse and their disclosure of abuse. Factors that influence disclosure for other populations are well articulated in the literature however, these factors have not been adequately verified in persons of Mexican descent. Data are reported from in-depth interviews with 26 clients at a shelter and an outreach agency in a south Texas-Mexico border community. Semi-structured interview guide was used to elicit information over an 11 month period. A grounded theory ethnography approach was used to analyze data. Verification strategies and constant comparison techniques (e.g. investigator responsiveness, methodological coherence, sampling adequacy, an active analytic stance, and saturation) enhanced rigor of analysis. Nineteen Mexican immigrant women and seven Mexican American women participated in the study. Several themes were discerned related to women's experiences in abuse: painful living, questioning endurance, and confronting reality. In almost every participant's account there was a description of repeated victimization by her intimate partner or partners, and again, by others within and outside her network. The participants discussed several cultural factors (e.g. embarrassment, concerns for family, avoidance of causing pain to family, protection of partner, avoidance of being judged) that hindered their decisions whether or not to disclose. Participants noted that healthcare workers rarely asked probing questions regarding abuse. The timing and process of disclosure took many turns for women in this study. Some of the factors hindering women from disclosing were found to be influenced by cultural practices. The consequences of disclosure for many of the women led them to re-victimization. Implications for practice to avoid missed opportunities with women living in abuse are to: ask questions routinely to encourage disclosure of abuse and offer community resource information for women living in abuse or both.^

Comparison of hand hygiene evaluations: A literature review

Background. Because our hands are the most common mode of transmission for bacteria causing hospital acquired infections, hand hygiene practices are the most effective method of preventing the spread of these pathogens, limiting the occurrence of healthcare-associated infections and reducing transmission of multi-drug resistant organisms. Yet, compliance rates are below 40% on the average. ^ Objective. This culminating experience project is primarily a literature review on hand hygiene to help determine the barriers to hand hygiene compliance and offer solutions on improving these rates and to build on a hand hygiene evaluation performed during my infection control internship completed at Memorial Hermann Hospital during the fall semester of 2005. ^ Method. A review of peer-reviewed literature using Ovid Medline, Ebsco Medline and PubMed databases using keywords: hand hygiene, hand hygiene compliance, alcohol based handrub, healthcare-associated infections, hospital-acquired infections, and infection control. ^ Results. A total of eight hand hygiene studies are highlighted. At a children's hospital in Seattle, hand hygiene compliance rates increases from 62% to 81% after five periods of interventions. In Thailand, 26 nurses dramatically increased compliance from 6.3% to 81.2% after just 7 months of training. Automated alcohol based handrub dispensers improved compliance rates in Chicago from 36.3% to 70.1%. Using education and increased distribution of alcohol based handrubs increased hand hygiene rates from 59% to 79% for Ebnother, from 54% to 85% for Hussein and from 32% to 63% for Randle. Spartanburg Regional Medical Center increased their rates from 72.5% to 90.3%. A level III NICU achieved 100% compliance after a month long educational campaign but fell back down to its baseline rate of 89% after 3 months. ^ Discussion. The interventions used to promote hand hygiene in the highlighted studies varied from low tech approaches such as printed materials to advanced electronic gadgets that alerted individuals automatically to perform hand hygiene. All approaches were effective and increased compliance rates. Overcoming hand hygiene barriers, receiving and accepting feedback is the key to maintaining consistently high hand hygiene adherence. ^

Evaluating the Harris County TexHealth 3-Share Plan: An exploratory study

An important health issue in the United States today is the large number of people who have problems accessing needed health care because they lack health insurance coverage. Providing health insurance coverage for the working uninsured is a particularly significant challenge in Texas, which has the highest percentage of uninsured in the nation. In response to the low rate of employer-sponsored coverage in the Houston area and the growing numbers of uninsured, the Harris County Health Care Alliance (HCHA) developed and implemented the Harris County 3-Share Plan. A 3-Share Plan is not insurance, but provides health coverage in the form of a benefits package to employers who subscribe to the program and offer it to their employees. ^ A cross sectional study design was conducted to describe 3-Share employer and employee participants and evaluate their outcomes after its first year of operation. Between September and December 2011, 85% of employers enrolled in the 3-Share Plan completed a survey about the affordability of the 3-Share Plan, their satisfaction with the Plan, and the Plan's impact on employee recruitment, retention, productivity, and absenteeism. Forty-five percent of employees enrolled in the 3-Share Plan responded to a survey asking about the affordability of the 3-Share plan, accessibility of health care, availability of providers on the plan, health plan availability, utilization of primary care providers and the ER, and satisfaction with the plan. ^ A summary of the findings shows employers and employees say that they joined the plan because of the low-cost, and once they had participated in the Plan, the majority of employers and employees found that it is affordable for them. The majority of employees say they are getting access easily and without delay, but for those who aren't able to get access, or are delayed, the main cause is related to non-financial barriers to care. Ultimately, employees are satisfied with the 3-Share, and they plan to continue with health coverage under the 3-Share Plan. The 3-Share Plan will keep people in a system of care, and promote health, which will benefit the individuals, the businesses and the community of Harris County.^

Evaluating the Harris County TexHealth 3-Share plan: An exploratory study

An important health issue in the United States today is the large number of people who have problems accessing needed health care because they lack health insurance coverage. Providing health insurance coverage for the working uninsured is a particularly significant challenge in Texas, which has the highest percentage of uninsured in the nation. In response to the low rate of employer-sponsored coverage in the Houston area and the growing numbers of uninsured, the Harris County Health Care Alliance (HCHA) developed and implemented the Harris County 3-Share Plan. A 3-Share Plan is not insurance, but provides health coverage in the form of a benefits package to employers who subscribe to the program and offer it to their employees. ^ A cross sectional study design was conducted to describe 3-Share employer and employee participants and evaluate their outcomes after its first year of operation. Between September and December 2011, 85% of employers enrolled in the 3-Share Plan completed a survey about the affordability of the 3-Share Plan, their satisfaction with the Plan, and the Plan's impact on employee recruitment, retention, and productivity. Forty-five percent of employees enrolled in the 3-Share Plan responded to a survey asking about the affordability of the 3-Share plan, accessibility of providers on the plan, satisfaction, and utilization of primary care providers and the ER. ^ A summary of the findings shows employers and employees say that they joined the plan because of the low-cost, and once they had participated in the Plan, the majority of employers and employees found that it is affordable for them. The majority of employees say they are getting access easily and without delay, but for those who aren't able to get access, or are delayed, the main cause is related to non-financial barriers to care. Ultimately, employees are satisfied with the 3-Share, and they plan to continue with health coverage under the 3-Share Plan. The 3-Share Plan will keep people in a system of care, and promote health, which will benefit the individuals, the businesses and the community of Harris County.^