Searching for the ideal DNA recognition code of covalent ligands

The combitiatorial approach restriction endonuclease protection selection and amplification REPSA was successfully used to determine ideal DNA interactions sites of covalent ligands. Unlike most other combinatorial methods, REPSA is based on inhibition of enzymatic cleavage by specific ligand-DNA complexes, which enables identification of binding sites of various ligands. However, the inherent nature of this technique posses a problem during selection of binding sites of covalent ligands. By modifying the technique according to the nature of the ligand, we demonstrate the flexibility of REPSA in identifying the preferred binding sites for monocovalent ligands, topoisomerase I and tallimustine, and the bicovalent ligand topoisomerase II. From among the preferred binding sites, we identified the consensus binding sequence of camptothecin induced topoisomerase I cleavage as ‘aGWT/Gc’, and tallimustine consensus sequences as ‘GTTCTA’ and ‘TTTTTTC’. We have shown for the first time that preferential binding of tallimustine occurs at sequences not previously reported. Furthermore, our data indicate that tallimustine is a novel DNA minor groove, guanine-specific alkylating agent. ^ Additionally, we have demonstrated in vivo that sequence-specific covalent DNA-binding small molecules have the ability to regulate transcription by inhibiting RNA polymerase II. Tallimustine, binding to its preferred sequences located in the 5′ untranslated region were an effective impediment for transcribing polymerase II. The ability of covalent binding small molecules to target predetermined DNA sequences located downstream of the promoter suggests a general approach for regulation of gene expression. ^

A practice-based culminating experience with Texas Children's Hospital: A hospital's journey to baby-friendly status

Breastfeeding and the use of human milk are widely accepted as the most complete form of nutrition for infants. Breastfeeding is shown to be associated with many positive health outcomes for both infants and mothers. Healthy People 2000 goals to increase breastfeeding rates in the early postpartum period to 75% fell short, with only 64% of mothers meeting this objective. Lack of support from healthcare providers, and unsupportive hospital policies and practices are noted as barriers to the initiation and duration of breastfeeding. The purpose of this study was to evaluate implementation of the BFHI Ten Steps to Successful Breastfeeding at Texas Children's Hospital. ^ The Baby-Friendly Hospital Initiative (BFHI) was developed in 1991 by the World Health Organization and the United Nations Children's Fund (UNICEF) to ensure that healthcare facilities offering maternity services adhere to the Ten Steps of Successful Breastfeeding and the International Code of Marketing of Breast-Milk Substitutes, and create legislation to protect the rights of breastfeeding women. The instrument used in this study was the BFHI 100 Assessment Tool created by Dr. Laura Haiek, Director of Public Health in Monteregie, Quebec, and her staff at Health and Social Services Agency of Quebec. The BFHI 100 tool utilizes 100 different indicators of compliance with BFHI through questionnaires administered to staff and administrators, pregnant and postpartum mothers, and an observer. ^ The study concluded that although there is much room for improvement in educating breastfeeding mothers, overall, the mothers interviewed were satisfied with their level of care in regards to breastfeeding support. Areas of improvement include staff training, as some nursing staff admitted to relying on the lactation consultants to provide most of the breastfeeding education for mothers. Only a small percentage of mothers interviewed reported that their baby “roomed-in” on average of 22 hours per day during their hospital stay. Staff encouragement of the rooming-in practice will help to increase the proportion of mothers who allow their babies to room-in. The current breastfeeding policy will also need to be revised and strengthened to be compliant with the Ten Steps. Ideally, Baby-Friendly practices will become the norm after staff are trained and policy revisions are made. Staff training and acceptance of breastfeeding as optimal nutrition for infants are the most critical factors that will ultimately drive change for the organization. ^

What's Working in Family-Based Services--or, What's Left to Believe in During a Time of Such Doubt?

This article is a qualitative, personal report from the field, designed to highlight current developments in family-based theory and practice that bring hopefulness to workers and clients. The author, an experienced human services consultant and family therapist, draws from his recent experience in a number of states to identify exemplars of practice in the following areas: integrative theory building, functional family assessment, systems change in regard to inter-agency coordination and foster care, community building in low income neighborhoods, developing humility as helpers, and addressing issues of hope and spirituality with clients and with co-workers. Given the turbulent and hostile political environment for family-based services, this article challenges us to remember that effectiveness in helping others is directly related to our feelings of hopefulness about ourselves and our world.

Folklore, fad, and fashion: The concept of misconduct in science redefined

This study is an analytical investigation of the nature and implications of the current conceptions of scientific misconduct, arguing that the question of what constitutes misconduct in science is significantly more complex than what conventionally has been believed. Complicating the definitions of misconduct are the differences between professional science and non-scientific professions, in their respective norms of what constitutes valid knowledge, and what counts as appropriate and inappropriate practice. While institutionalized science claims that there is clear differentiation between its standards of validity and those of the non-scientific professions, this paper argues that, when it comes to misconduct, the perceived boundaries between the scientific and non-scientific professions are breached; the practice standards that science currently employs in self-policing misconduct have come to resemble the minimal juridical standards of practice that other professions employ. This study attempts, despite erosion of these traditional boundaries, to move from legalistic standards of scientific practice to intramural standards of practice, and in so doing, to hold scientific practice to a higher standard than ordinary public conduct. The result is a clearer understanding of scientific misconduct to aid those individual scientists who are required to make onerous determinations about the appropriateness of specific practices by their peers. ^

Nutrition knowledge and attitudes of physician assistants in Texas

Physician Assistants (PAs) are increasingly assuming more responsibilities as "front-line" health providers due to emphasis on primary care and cost-containment in the rapidly changing health care environment. Nutrition plays an important role in health promotion and disease prevention. Primary care providers, including PAs, have enormous potential as nutrition counselors and advocates. There have been no studies to date that address the PAs' adequacy of nutrition education or their attitudes toward the value of nutrition. Therefore, it was the purpose of the study to determine the nutrition knowledge and attitudes of PAs in Texas.^ All certified physician assistants in Texas were eligible for the study. A mailed survey was sent to 1,482 PAs in Texas with a response rate of 54.2%. The sample utilized for data analysis was 764 PAs.^ The study compared the nutrition knowledge mean scores for PAs who graduated from a PA program greater than 11 years ago with those who graduated less than 11 years ago. The study also examined Texas PAs' attitudes about their nutrition education training, the value of nutrition counseling, and their perceived ability to provide such nutrition counseling. Demographic and practice information was collected from the PAs. Demographically, PAs in Texas were found to be comparable to the national population of PAs surveyed in 1996.^ The overall mean level of nutrition knowledge was 70% correct. The mean level of nutrition knowledge was significantly related to the type of PA program that the PA graduated from (i.e., Certificate only or Master's degree level). No significant relationships were found between the mean nutrition knowledge score and age, year of graduation, length of practice, or the type of nutrition education provided in PA program.^ The majority of the PAs surveyed felt that diet and nutrition has an important role in disease prevention and felt that PA programs should place a greater emphasis on nutrition education. Many PAs surveyed were not satisfied with the amount of nutrition education they had received in their PA education programs and were not confident in their ability to provide nutrition counseling to patients.^ Suggestions are offered for improvement in PA nutrition education in the areas of both nutrition knowledge and patient counseling skills. In addition, this study recommends developing and strengthening partnerships between PAs and nutrition organizations. ^

Policy analysis of Texas Senate Bill 532 and the regulation of nurse practitioners in the convenience care model

Background. Retail clinics, also called convenience care clinics, have become a rapidly growing trend since their initial development in 2000. These clinics are coupled within a larger retail operation and are generally located in "big-box" discount stores such as Wal-mart or Target, grocery stores such as Publix or H-E-B, or in retail pharmacies such as CVS or Walgreen's (Deloitte Center for Health Solutions, 2008). Care is typically provided by nurse practitioners. Research indicates that this new health care delivery system reduces cost, raises quality, and provides a means of access to the uninsured population (e.g., Deloitte Center for Health Solutions, 2008; Convenient Care Association, 2008a, 2008b, 2008c; Hansen-Turton, Miller, Nash, Ryan, Counts, 2007; Salinsky, 2009; Scott, 2006; Ahmed & Fincham, 2010). Some healthcare analysts even suggest that retail clinics offer a feasible solution to the shortage of primary care physicians facing the nation (AHRQ Health Care Innovations Exchange, 2010). ^ The development and performance of retail clinics is heavily dependent upon individual state policies regulating NPs. Texas currently has one of the most highly regulated practice environments for NPs (Stout & Elton, 2007; Hammonds, 2008). In September 2009, Texas passed Senate Bill 532 addressing the scope of practice of nurse practitioners in the convenience care model. In comparison to other states, this law still heavily regulates nurse practitioners. However, little research has been conducted to evaluate the impact of state laws regulating nurse practitioners on the development and performance of retail clinics. ^ Objectives. (1). To describe the potential impact that SB 532 has on retail clinic performance. (2). To discuss the effectiveness, efficiency, and equity of the convenience care model. (3). To describe possible alternatives to Texas' nurse practitioner scope of practice guidelines as delineated in Texas Senate Bill 532. (4). To describe the type of nurse practitioner state regulation (i.e. independent, light, moderate, or heavy) that best promotes the convenience care model. ^ Methods. State regulations governing nurse practitioners can be characterized as independent, light, moderate, and heavy. Four state NP regulatory types and retail clinic performance were compared and contrasted to that of Texas regulations using Dunn and Aday's theoretical models for conducting policy analysis and evaluating healthcare systems. Criteria for measurement included effectiveness, efficiency, and equity. Comparison states were Arizona (Independent), Minnesota (Light), Massachusetts (Moderate), and Florida (Heavy). ^ Results. A comparative states analysis of Texas SB 532 and alternative NP scope of practice guidelines among the four states: Arizona, Florida, Massachusetts, and Minnesota, indicated that SB 532 has minimal potential to affect the shortage of primary care providers in the state. Although SB 532 may increase the number of NPs a physician may supervise, NPs are still heavily restricted in their scope of practice and limited in their ability to act as primary care providers. Arizona's example of independent NP practice provided the best alternative to affect the shortage of PCPs in Texas as evidenced by a lower uninsured rate and less ED visits per 1,000 population. A survey of comparison states suggests that retail clinics thrive in states that more heavily restrict NP scope of practice as opposed to those that are more permissive, with the exception of Arizona. An analysis of effectiveness, efficiency, and equity of the convenience care model indicates that retail clinics perform well in the areas of effectiveness and efficiency; but, fall short in the area of equity. ^ Conclusion. Texas Senate 532 represents an incremental step towards addressing the problem of a shortage of PCPs in the state. A comparative policy analysis of the other four states with varying degrees of NP scope of practice indicate that a more aggressive policy allowing for independent NP practice will be needed to achieve positive changes in health outcomes. Retail clinics pose a temporary solution to the shortage of PCPs and will need to expand their locations to poorer regions and incorporate some chronic care to obtain measurable health outcomes. ^