Synthesis of (-)-PNU-286607 by asymmetric cyclization of alkylidene barbiturates.

PNU-286607 is the first member of a promising, novel class of antibacterial agents that act by inhibiting bacterial DNA gyrase, a target of clinical significance. Importantly, PNU-286607 displays little cross-resistance with marketed antibacterial agents and is active against methicillin-resistant staphylococcus aureus (MRSA) and fluoroquinoline-resistant bacterial strains. Despite the apparent stereochemical complexity of this unique spirocyclic barbituric acid compound, the racemic core is accessible by a two-step route employing a relatively obscure rearrangement of vinyl anilines, known in the literature as the "tert-amino effect." After a full investigation of the stereochemical course of the racemic reaction, starting with the meso cis-dimethylmorpholine, a practical asymmetric variant of this process was developed.

Organizational and individual perspectives on caring in hospitals.

Caring and humanism in hospitals exist on both the organizational and the individual levels. This paper identifies key organizations and foundations that have succeeded in promoting or fostering caring environments in hospitals. These include the Picker Institute, the Baptist Healing Trust, Sage Consulting, and the Caritas Consortium. Exemplary, caring clinicians in hospitals are also described. These clinicians developed positive relationships with patients and in interviews communicated a number of approaches to express caring to patients. Health and human services managers can take a number of steps to promote caring among their clinicians. However, they must implement a culture and a reward system that encourages humanism.

Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors.

QPT-1 was discovered in a compound library by high-throughput screening and triage for substances with whole-cell antibacterial activity. This totally synthetic compound is an unusual barbituric acid derivative whose activity resides in the (-)-enantiomer. QPT-1 had activity against a broad spectrum of pathogenic, antibiotic-resistant bacteria, was nontoxic to eukaryotic cells, and showed oral efficacy in a murine infection model, all before any medicinal chemistry optimization. Biochemical and genetic characterization showed that the QPT-1 targets the beta subunit of bacterial type II topoisomerases via a mechanism of inhibition distinct from the mechanisms of fluoroquinolones and novobiocin. Given these attributes, this compound represents a promising new class of antibacterial agents. The success of this reverse genomics effort demonstrates the utility of exploring strategies that are alternatives to target-based screens in antibacterial drug discovery.

Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics.

The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein.

Establishing values-based leadership and value systems in healthcare organizations.

The importance of values in organizations is often discussed in management literature. Possessing strong or inspiring values is increasingly considered to be a key quality of successful leaders. Another common theme is that organizational values contribute to the culture and ultimate success of organizations. These conceptions or expectations are clearly applicable to healthcare organizations in the United States. However, healthcare organizations have unique structures and are subject to societal expectations that must be accommodated within an organizational values system. This article describes theoretical literature on organizational values. Cultural and religious influences on Americans and how they may influence expectations from healthcare providers are discussed. Organizational cultures and the training and socialization of the numerous professional groups in healthcare also add to the considerable heterogeneity of value systems within healthcare organizations. These contribute to another challenge confronting healthcare managers--competing or conflicting values within a unit or the entire organization. Organizations often fail to reward members who uphold or enact the organization's values, which can lead to lack of motivation and commitment to the organization. Four key elements of values-based leadership are presented for healthcare managers who seek to develop as values-based leaders. 1) Recognize your personal and professional values, 2) Determine what you expect from the larger organization and what you can implement within your sphere of influence, 3) Understand and incorporate the values of internal stakeholders, and 4) Commit to values-based leadership.

The Caring Professionals Program: educational approaches that integrate caring attitudes and empathic behaviors into health professions education.

Caring attitudes and empathic behaviors are considered by most Americans to be an essential and intrinsic element of appropriate health care, yet little attention is given to this in the curricula of most healthcare professional training programs. This paper describes an ongoing educational intervention to develop healthcare professionals with caring attitudes and empathic behaviors that will be sustained in their professional practice environments. The Caring Professionals Program was designed to enhance and redesign existing learning experiences in four academic programs: physical therapy, occupational therapy, physician assistant, and nurse practitioner. Students entering in the summer of 2009 were engaged in the initial program and study. Six educational elements were employed in the Caring Professionals Program: experience, reflection, problem-solving, didactic, active participation, and role modeling. Educational interventions were designed to be appropriate to the students' temporal progress through their programs, specifically the early, middle or late stages. The Caring Professionals Program may serve as a model for other allied health schools and also contribute to a college culture that supports caring and humanism.

Racial and ethnic comparisons of nursing home residents at admission.

OBJECTIVE: To present racial/ethnic comparisons of comprehensive profiles of nursing home residents at admission, including whites, African Americans, Hispanics, Asians/Pacific Islanders, and American Indians/Alaska Natives. METHODS: More than 885,000 admission assessments recorded in the national Minimum Data Set (MDS) were analyzed. Racial and ethnic analyses of the MDS admission assessments were conducted using the software package SAS. RESULTS: There were significant racial/ethnic differences in gender and age, with minority residents more likely to be male and younger. African American, Hispanic, and Asian/Pacific Islanders were significantly more likely than white residents to exhibit total dependence in the self-performance of the ADLs and to have greater cognitive impairments, with Asian/Pacific Islanders the most physically dependent and cognitively impaired. DISCUSSION: The results illustrate significant and substantive differences among the racial/ethnic groups for many demographic characteristics, as well as health-related indicators and conditions. This analysis suggests that the general perspective that economically disadvantaged minorities enter nursing homes in worse condition than whites is too simplistic. More research, particularly qualitative studies of specific minority groups, will advance our understanding of why members of some racial/ethnic groups require nursing home placement sooner than other groups.

Compassionate clinicians: take patient care beyond the ordinary.

This study sought to identify specific actions, interventions, and interpersonal relationships with patients exhibited by a group of compassionate healthcare clinicians. Researchers interviewed 24 hospital clinicians who were identified by administrators as being exemplary in caring and compassion. Analysis of qualitative data indicated that the clinicians do not attempt to distance themselves, but develop warm, empathic relationships with patients. Participating clinicians did not appear to sacrifice objectivity in practicing compassionate care, but were able to integrate the mind and heart in their work. Based on the qualitative analyses, researchers developed a preliminary model of affective clinician/patient interactions.

Human and ecosystem health: the environment-agriculture connection in developing countries.

Agricultural productivity and the health of farming populations are both influenced by environmental change. Farming activities also affect the environment. Six principal dimensions of this agriculture/environment interrelation are explored: water resources; erosion and nonpoint source pollution; pesticides and fertilizers; deforestation; population pressures; and biodiversity. Changes in these environmental dimensions are critical to the health of rural populations in developing countries. National and international policies and incentives for the protection of agricultural environments are described.