Hsp110 chaperones control client fate determination in the hsp70-Hsp90 chaperone system.

Heat shock protein 70 (Hsp70) plays a central role in protein homeostasis and quality control in conjunction with other chaperone machines, including Hsp90. The Hsp110 chaperone Sse1 promotes Hsp90 activity in yeast, and functions as a nucleotide exchange factor (NEF) for cytosolic Hsp70, but the precise roles Sse1 plays in client maturation through the Hsp70-Hsp90 chaperone system are not fully understood. We find that upon pharmacological inhibition of Hsp90, a model protein kinase, Ste11DeltaN, is rapidly degraded, whereas heterologously expressed glucocorticoid receptor (GR) remains stable. Hsp70 binding and nucleotide exchange by Sse1 was required for GR maturation and signaling through endogenous Ste11, as well as to promote Ste11DeltaN degradation. Overexpression of another functional NEF partially compensated for loss of Sse1, whereas the paralog Sse2 fully restored GR maturation and Ste11DeltaN degradation. Sse1 was required for ubiquitinylation of Ste11DeltaN upon Hsp90 inhibition, providing a mechanistic explanation for its role in substrate degradation. Sse1/2 copurified with Hsp70 and other proteins comprising the "early-stage" Hsp90 complex, and was absent from "late-stage" Hsp90 complexes characterized by the presence of Sba1/p23. These findings support a model in which Hsp110 chaperones contribute significantly to the decision made by Hsp70 to fold or degrade a client protein.

Border intervention by Promotores for type 2 diabetes

Purpose of the study. This study had two components. The first component of the study was the development and implementation of an infrastructure that integrated Promotores who teach diabetes self-management into a community clinic. The second component was a six-month randomized clinical trial (RCT) designed to test the effectiveness of the Promotores in changing knowledge, beliefs, and HbA1c levels among Mexican American patients with type 2 diabetes. ^ Methods. Starfield's adaptation of the Donbedian structure, process, and outcome methodology was used to develop a clinic infrastructure that allowed the integration of Promotores as diabetes educators. The RCT of the culturally sensitive Promotores-led 10-week diabetes self-management program compared the outcomes of 63 patients in the intervention group with 68 patients in a wait-list, usual care control group. Participants were Mexican Americans, at least 18 years of age, with type 2 diabetes, who were patients at a Federally Qualified Health Center on the Texas-Mexico border. At baseline, three months, and six months, data were collected using the Diabetes Knowledge Questionnaire (DKQ, the Health Beliefs Questionnaire (HBQ, and HbA1c levels were drawn by the clinic laboratory. A mixed model methodology was used to analyze the data. ^ Results. The infrastructure to support a Promotores-led diabetes self-management course designed in concert with administration, the physicians, and the CDE, resulted in (1) employment of Promotores to teach diabetes self-management courses; (2) integration of provider and nurse oversight of course design and implementation; (3) management of Promotora training, and the development of teaching competencies and skills; (4) coordination of care through communication and documentation policies and procedures; (5) utilization of quality control mechanisms to maintain patient safety; and (6) promotion of a culturally competent approach to the educational process. The RCT resulted in a significant improvement in the intervention group's DKQ scores over time (F [1, 129] = 4.77, p = 0.0308), and in treatment by time (F [2, 168] = 5.85, p = 0.0035). Neither the HBQ scores nor the HbA1c changed over time. However, the baseline HbA1c was 7.49, almost at the therapeutic level. The DKQ, HBQ, and HbA1c results were significantly affected by age; the DKQ and HbA1c by years with diabetes. ^ Conclusions. The clinic model provides a systematic approach to safely address the educational needs of large numbers of patients with type 2 diabetes who live in communities that suffer from a lack of health care professionals. The Promotores-led diabetes self-management course improved the knowledge of patients with diabetes and may be a culturally sensitive strategy for meeting patient educational needs. The low baseline HbA1c levels in this border community suggested that patients in this Federally Qualified Health Center on the Texas-Mexico border were experiencing good medical management of their diabetes. ^

A comparative analysis of hospital -based physician monitoring systems

The purpose of the multiple case-study was to determine how hospital subsystems (such as physician monitoring and credentialing; quality assurance; risk management; and peer review) were supporting the monitoring of physicians? Three large metropolitan hospitals in Texas were studied and designated as hospitals #1, #2, and #3. Realizing that hospital subsystems are a unique entity and part of a larger system, conclusions were made on the premises of a quality control system, in relation to the tools of government (particularly the Health Care Quality Improvement Act (HCQIA)), and in relation to itself as a tool of a hospital.^ Three major analytical assessments were performed. First, the subsystems were analyzed as to their "completeness"; secondly, the subsystems were analyzed for "performance"; and thirdly, the subsystems were analyzed in reference to the interaction of completeness and performance.^ The physician credentialing and monitoring and the peer review subsystems as quality control systems were most complete, efficient, and effective in hospitals #1 and #3. The HCQIA did not seem to be an influencing factor in the completeness of the subsystem in hospital #1. The quality assurance and risk management subsystem in hospital #2 was not representative of completeness and performance and the HCQIA was not an influencing factor in the completeness of the Q.A. or R.M. systems in any hospital. The efficiency (computerization) of the physician credentialing, quality assurance and peer review subsystems in hospitals #1 and #3 seemed to contribute to their effectiveness (system-wide effect).^ The results indicated that the more complete, effective, and efficient subsystems were characterized by (1) all defined activities being met, (2) the HCQIA being an influencing factor, (3) a decentralized administrative structure, (4) computerization an important element, and (5) staff was sophisticated in subsystem operations. However, other variables were identified which deserve further research as to their effect on completeness and performance of subsystems. They include (1) medical staff affiliations, (2) system funding levels, (3) the system's administrative structure, and (4) the physician staff "cultural" characteristics. Perhaps by understanding other influencing factors, health care administrators may plan subsystems that will be compatible with legislative requirements and administrative objectives. ^