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A wide variety of speech processing strategies for multichannel auditory prostheses were compared in studies of two patients implanted with the UCSF electrode array. Each strategy was evaluated using tests of vowel and consonant confusions, with and without lipreading. Included among the strategies were the compressed analog processor of the present UCSF/Storz prosthesis and a group of interleaved pulses processors in which the amplitudes of nonsimultaneous pulses code the spectral variations of speech. For these patients, each with indications of poor nerve survival, test scores were significantly higher with the interleaved pulses processors. We believe this superior performance was a result of 1. the substantial release from channel interactions provided by nonsimultaneous stimuli and 2. a fast enough rotation among the channels to support adequate temporal and spectral resolution of perceived speech sounds. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in the April 7, 1989 issue of the 'Journal of the American Medical Association,' noting the adequacy of continuous hyperchlorination of plumbing systems in the prevention of colonization and replication of Legionella in potable water.

Introduction: Acute inflammatory demyelinating polyneuropathy (AIDP) is characterized by progressive, mild sensory symptoms and progressive areflexic weakness. It typically follows a gastrointestinal or respiratory infection but has rarely been described after acute viral hepatitis., Case Report: This is the case of a 59-year-old male who presented to the emergency department after acutely developing progressive neurologic symptoms following a hospitalization for acute hepatitis A. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, and cervical spine magnetic resonance imaging revealed nerve root enhancement., Discussion: The patient was diagnosed with AIDP, which is the most common subtype of Guillain-Barré syndrome in the United States and Europe. There have been few previously reported cases of AIDP following acute hepatitis A infection.

Introduction: Patient safety (PS) is one of the most important priorities in modern healthcare systems. Unfortunately, PS education is limited in many medical school curricula. Our objective was to implement an innovative curriculum to introduce third-year medical students on their pediatric clerkship to PS concepts and domains, and to provide a safe environment to discuss lapses in PS that they identified while caring for patients., Methods: At the start of the pediatric clerkship, students were introduced to the curriculum, instructed to identify a lapse of PS, and to submit a description and analysis of the lapse using the SAFE framework (S = Safety concern, A = Action taken, F = Failure, linked to safety domains, E = Effects on patient outcome). Two sessions, 90-mins each, were conducted every clerkship during which there was a brief didactic presentation, each student presented their case, and the case discussed by students and faculty., Results: Over 19 months, 75 students participated. The most common PS themes identified were Communication (57% of cases), Human factors (39%), and System issues (37%). Anonymous written feedback was obtained; learners reported improved knowledge and ability to identify lapses in PS and to propose potential solutions to prevent similar future events. They expressed a desire for additional PS and quality improvement education., Discussion: Our results show that third-year medical students are able to identify lapses in PS and able to propose solutions. This aligns with the Association of American Medical Colleges (AAMC) goals of entrustable professional activities (EPA) 13. We intend to expand the curriculum to other third-year core clerkships., Competing Interests: Declaration of conflicting interests:MA declares that she is a shareholder in CGN Global. There are no other potential conflicts of interest to disclose.

Progesterone receptor (PR), a member of the nuclear receptor superfamily, is a key regulator of several processes in reproductive function. We have studied the dynamics of the interaction of PR with a natural target promoter in living cells through the use of fluorescence recovery after photobleaching (FRAP) analysis and also have characterized the dynamics of the interaction of PR with the mouse mammary tumor virus (MMTV) promoter reconstituted into chromatin in vitro. In photobleaching experiments, PR in the presence of the agonist R5020 exhibits rapid exchange with the MMTV promoter in living cells. Two PR antagonists, RU486 and ZK98299, have opposite effects on receptor dynamics in vivo. In the presence of RU486, PR binds to the promoter and is exchanged more slowly than the agonist-activated receptor. In contrast, PR bound to ZK98299 is not localized to the promoter and exhibits higher mobility in the nucleoplasm than the agonist-bound receptor. Significantly, PR bound to R5020 or RU486 can recruit the SWI/SNF chromatin remodeling complex to the promoter, but PR activated with ZK98299 cannot. Furthermore, we found ligand-specific active displacement of PR from the MMTV promoter during chromatin remodeling in vitro and conclude that the interaction of PR with chromatin is highly dynamic both in vivo and in vitro. We propose that factor displacement during chromatin remodeling is an important component of receptor mobility and that ligand-specific interactions with remodeling complexes can strongly influence receptor nuclear dynamics and rates of exchange with chromatin in living cells.

An ultrafast UV laser crosslinking assay has provided novel insights into the progression of the SWI/SNF-mediated chromatin-remodeling reaction and transcription factor binding in real time. We demonstrate site-specific crosslinking between the glucocorticoid receptor (GR), the hSWI/SNF chromatin-remodeling complex, and the mouse mammary tumor virus (MMTV) promoter assembled in an array of correctly positioned nucleosomes. GR first demonstrates rapid binding to the promoter and then is actively displaced from the template during the remodeling reaction. This displacement reaction requires the hSWI/SNF complex and ATP, is specific to the nucleoprotein template, and is accompanied by a core histone rearrangement. The hSWI/SNF complex associates with random positions on the chromatin template in the absence of GR but is recruited specifically to the B/C region when GR is included. These results indicate that enhancement of hSWI/SNF-mediated factor accessibility, a hallmark of chromatin remodeling, is in some cases transient, reversible, and periodic.

Chromatin remodeling by the glucocorticoid receptor (GR) is associated with activation of transcription at the mouse mammary tumor virus (MMTV) promoter. We reconstituted this nucleoprotein transition with chromatin assembled on MMTV DNA. The remodeling event was ATP dependent and required either a nuclear extract from HeLa cells or purified human Swi/Snf. Through the use of a direct interaction assay (magnetic bead pull-down), we demonstrated recruitment of human Swi/Snf to MMTV chromatin by GR. Unexpectedly, we found that GR is actively displaced from the chromatin template during the remodeling process. ATP-dependent GR displacement was reversed by the addition of apyrase and was specific to chromatin templates. The disengagement reaction could also be induced with purified human Swi/Snf. Although GR apparently dissociated during chromatin remodeling by Swi/Snf, it participated in binding of the secondary transcription factor, nuclear factor 1. These results are paralleled by a recent discovery that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment in living cells. Both the in vitro and in vivo results are consistent with a dynamic model (hit and run) in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, facilitates transcription factor binding, and is simultaneously lost from the template.

Introduction: Recent changes by the Health Care Financing Administration (HCFA) have resulted in decreased Medicare support for emergency medicine (EM) residencies., Objective: To determine the effects of reduced graduate medical education (GME) funding support on residency size, resident rotations, and support for a fourth postgraduate year (PGY) of training and for residents with previous training., Methods: A 36-question survey was developed by the Council of Emergency Medicine Residency Directors (CORD) committee on GME funding and sent to all 122 EM program directors (PDs). Responses were collected by the Society for Academic Emergency Medicine (SAEM) office and blinded with respect to the institution., Results: Of 122 programs, 109 (89%) responded, of which 78 were PGY 1-3 programs, 19 were PGY 2-4, and 12 were PGY 1-4. The PDs were asked specifically whether there were changes in program size due to changes in Medicare reimbursement. Although few programs (12%) decreased their size or planned to decrease their size, 39% had discussions regarding decreasing their size. Thirty percent of the PDs responded that other programs at their institution had already decreased their size; 26% of the PDs had problems with financing outside rotations; and 24% had a decrease in off-service residents in their emergency departments (EDs). Only seven (6%) of programs paid residents from practice plan dollars, while most (82%) were fully supported by federal GME funding. Nearly all four-year programs (97%) received full resident salary support from their institutions and 77% of programs accept residents with previous training., Conclusions: Nearly all EM programs are fully supported by their institutions, including the fourth postgraduate year. Most programs take residents with previous training. Although few programs have reduced their size, many are discussing this. Many programs have had difficulty with funding off-service rotations and many have had decreased numbers of off-service residents in their EDs. Recent GME funding changes have had adverse effects on EM residency programs.

Regulatory agencies increasingly require hospitals to provide evidence of employee compliance with mandated competencies. This article provides information on the innovative use of Intranet-delivered computer-based training as an effective and efficient method of providing and documenting training to meet regulatory requirements. The authors discuss the advantages and disadvantages of Intranet-based instructional modules, instruction on developing Intranet-based modules, and an example of a healthcare system that is effectively using intranet-based modules for competency training.

The glucocorticoid receptor interacting protein-1 (GRIP1) is a member of the steroid receptor coactivator (SRC) family of transcriptional regulators. Green fluorescent protein (GFP) fusions were made to full-length GRIP1, and a series of GRIP1 mutants lacking the defined regulatory regions and the intracellular distribution of these proteins was studied in HeLa cells. The distribution of GRIP1 was complex, ranging from diffuse nucleoplasmic to discrete intranuclear foci. Formation of these foci was dependent on the C-terminal region of GRIP1, which contains the two characterized transcriptional activation domains, AD1 and AD2. A subpopulation of GRIP1 foci associate with ND10s, small nuclear bodies that contain several proteins including PML, SP100, DAXX, and CREB-binding protein (CBP). Association with the ND10s is dependent on the AD1 of GRIP1, a region of the protein previously described as a CBP-interacting domain. The GRIP1 foci are enriched in components of the 26S proteasome, including the core 20S proteasome, PA28alpha, and ubiquitin. In addition, the irreversible proteasome inhibitor lactacystin induced an increase in the total fluorescence intensity of the GFP-GRIP1 expressing cells, demonstrating that GRIP1 is degraded by the proteasome. These findings suggest the intriguing possibility that degradation of GRIP1 by the 26S proteasome may be a key component of its regulation.

Activated steroid receptors induce chromatin remodeling events in the promoters of some target genes. We previously reported that transiently expressed progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMTV) promoter when it adopts the form of ordered chromatin. However, when expressed continuously, the PR acquires this ability. In this study we explored whether this gain of function occurs through alterations in nucleoprotein structure at the MMTV promoter or through changes in receptor status. We observed no major structural differences at the MMTV promoter in the presence of constitutively expressed PR and found its mechanism of activation to be very similar to that of the glucocorticoid receptor (GR). However, a systematic comparison of the functional behavior of the transiently and constitutively expressed PR elucidated significant differences. The transiently expressed PR is activated in the absence of ligand by cAMP and by components in FBS and has significantly increased sensitivity to progestins. In contrast, the constitutively expressed PR is refractory to activation by cAMP and serum and has normal sensitivity to its ligand. In addition, while the PR is localized to the nucleus in both cases, a significant fraction of the transiently expressed PR is tightly bound to the nucleus even in the absence of ligand, while the majority of constitutively expressed PR is not. These results strongly suggest that the PR undergoes processing in the cell subsequent to its initial expression and that this processing is important for various aspects of its function, including its ability to productively interact with target genes that require chromatin remodeling for activation.

The majority of skin trauma incidents cause minor injury that can be treated effectively in the outpatient setting. A new approach to the closure of skin lacerations using tissue adhesive is presented and the current management of abrasions, blisters, burns, skin tears, and subungual hematomas are reviewed. An overview of wound dressings is provided to assist in obtaining the optimal wound-healing environment.