Why some employees adopt or resist reorganization of work practices in health care: associations between perceived loss of resources, burnout, and attitudes to change.

In recent years, successive work reorganization initiatives have been implemented in many healthcare settings. The failure of many of these change efforts has often been attributed in the prominent management discourse to change resistance. Few studies have paid attention to the temporal process of workers' resource depletion/accumulation over time and its links with workers' psychological states and reactions to change. Drawing upon the conservation of resources theory, this study examines associations between workers' perceptions of loss of resources, burnout, and attitudes to change. The study was conducted in five health and social service centres in Quebec, in units where a work reorganization project was initiated. A prospective longitudinal design was used to assess workers' perceptions at two time points 12 months apart. Our findings are consistent with the conservation of resources theory. The analysis of latent differences scores between times 1 and 2 showed that the perceived loss of resources was associated with emotional exhaustion, which, in turn, was negatively correlated with commitment to change and positively correlated with cynicism. In confirming the temporal relationship between perceived loss of resources, occupational burnout, and attitude to change, this research offers a new perspective to explain negative and positive reactions to change implementation.

Measurement of readiness to reduce driving speed: a pilot study.

Speeding is a preventable risky behavior that contributes to risk of accident. Readiness to change reflects an individual's recognition of and desire to change behavior. No measure to identify readiness to change has yet been validated for speeding. The Readiness to Change Questionnaire appraises readiness to change drinking behavior. The questionnaire was adapted to speeding and its psychometric properties examined. Participants (N = 112) completed the questionnaire and reported their usual driving speed. A clear component structure and acceptable internal consistency and test-retest reliability were found. Convergent validity was indicated by an association between higher readiness to change and lower driving speed. Results support the questionnaire's potential as a measure of readiness to change speeding, and advance research into the role of motivation in speeding behavior.

Evaluation of VCH-759 monotherapy in hepatitis C infection.

BACKGROUND/AIMS: VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase with sub-micromolar IC(50) values versus genotype 1a/1b replicons. METHODS: The antiviral activity, pharmacokinetics and tolerability of VCH-759 administered as monotherapy for 10 days with a 14 day follow-up period were evaluated in 31 treatment-nai ve genotype 1 participants. Three cohorts received: 400mg thrice (t.i.d.), 800 mg twice (b.i.d.), 800 mg t.i.d or placebo. RESULTS: VCH-759 was well tolerated with the most frequent adverse event being gastrointestinal upset in both the active and placebo groups attributable, in part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma levels were at or above the IC(90) (non protein-adjusted) for all dosing regimens. The mean maximal decrease in HCV RNA log(10) (IU/mL) was 1.97, 2.30 and 2.46 for 400mg t.i.d., 800 mg b.i.d. and 800 mg t.i.d. doses. Viral polymerase genotypic sequencing revealed emergence of HCV variants in a majority of participants that coincided with on-treatment viral rebound. CONCLUSIONS: VCH-759 was well tolerated and achieved a> or =2 log(10) decline in HCV RNA with 800 mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was observed and associated with resistant variants. This data supports further evaluation of VCH-759 in combination with interferon-ribavirin treatment.

Non-nucleoside inhibitors binding to hepatitis C virus NS5B polymerase reveal a novel mechanism of inhibition.

The RNA-dependent RNA polymerase (NS5B) from hepatitis C virus (HCV) is a key enzyme in HCV replication. NS5B is a major target for the development of antiviral compounds directed against HCV. Here we present the structures of three thiophene-based non-nucleoside inhibitors (NNIs) bound non-covalently to NS5B. Each of the inhibitors binds to NS5B non-competitively to a common binding site in the "thumb" domain that is approximately 35 Angstroms from the polymerase active site located in the "palm" domain. The three compounds exhibit IC(50) values in the range of 270 nM to 307 nM and have common binding features that result in relatively large conformational changes of residues that interact directly with the inhibitors as well as for other residues adjacent to the binding site. Detailed comparisons of the unbound NS5B structure with those having the bound inhibitors present show that residues Pro495 to Arg505 (the N terminus of the "T" helix) exhibit some of the largest changes. It has been reported that Pro495, Pro496, Val499 and Arg503 are part of the guanosine triphosphate (GTP) specific allosteric binding site located in close proximity to our binding site. It has also been reported that the introduction of mutations to key residues in this region (i.e. Val499Gly) ablate in vivo sub-genomic HCV RNA replication. The details of NS5B polymerase/inhibitor binding interactions coupled with the observed induced conformational changes provide new insights into the design of novel NNIs of HCV.

Alveolar segmental sandwich osteotomy for anterior maxillary vertical augmentation prior to implant placement.

Over a 5-year period, 10 partially edentulous patients with anterior vertical maxillary deficiency were treated consecutively with segmental osteotomy and interpositional bone grafting prior to dental implant placement. Alveolar vertical projection and papillary form proved to be stable in all patients up to 5 years postsurgery. Implant aesthetic results were judged to be satisfactory. The technique is an alternative to alveolar distraction osteogenesis but is limited to a vertical increase of about 5 mm in the anterior maxilla.

Osseointegrated craniofacial implants in the rehabilitation of orbital defects: an update of a retrospective experience in the United States.

STATEMENT OF PROBLEM: Since their introduction, craniofacial implants have been used in prosthetic rehabilitation of facial defects. The literature, however, indicates marked variability in outcomes using implants for the retention of orbital prostheses. PURPOSE: A multicenter report updating the experience in the United States with the use of craniofacial implants for prosthetic rehabilitation of orbital defects is presented. MATERIAL AND METHODS: Surveys were sent to clinicians at 25 centers where maxillofacial prosthetic treatment is provided to obtain retrospective data regarding patients who completed implant-retained orbital prosthetic rehabilitation. Data on implant placement location, radiation treatment history, and use of hyperbaric oxygen therapy were collected and assessed in relationship to implant survival over time. The Kaplan-Meier life table and Wilcoxon analyses (alpha = .05) were used to assess the significance of the findings. RESULTS: Ten centers responded, providing data suitable for statistical analysis on 153 implants placed to retain 44 orbital prostheses and followed for a mean period of 52.6 months. Forty-one implant integration failures occurred during this follow-up period, resulting in an overall integration survival rate of 73.2%. No significant relationship was found between radiation treatment history, hyperbaric oxygen therapy history, or implant placement location and implant survival. Individual responses revealed large variability between reporting centers in treatment outcomes. CONCLUSION: Craniofacial implants may offer marked benefits in the prosthetic rehabilitation of orbital defects when compared to conventional adhesive retention designs. However, questions remain regarding long-term predictability and the impact specific factors may have on treatment outcomes. Insufficient data is currently available from which to draw statistically meaningful conclusions. The establishment of a national database designed to acquire adequate data to assess treatment outcomes is recommended.

Design and synthesis of a potent macrocyclic 1,6-naphthyridine anti-human cytomegalovirus (HCMV) inhibitors.

A novel class of macrocyclic 1,6-napthyridines designed to adopt the presumed bioactive conformation of anti-HCMV acyclic 1,6-napthyridines are described. Both 14- and 15-membered macrocycles were shown to be highly potent against HCMV HSV-1 and HSV-2.

Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors.

Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus (HCV) from two crystal forms have been determined. Similar to the three-dimensional structures of HCV polymerase genotype 1b and other known polymerases, the structures of the HCV polymerase genotype 2a in both crystal forms can be depicted in the classical right-hand arrangement with fingers, palm, and thumb domains. The main structural differences between the molecules in the two crystal forms lie at the interface of the fingers and thumb domains. The relative orientation of the thumb domain with respect to the fingers and palm domains and the beta-flap region is altered. Structural analysis reveals that the NS5B polymerase in crystal form I adopts a "closed" conformation that is believed to be the active form, whereas NS5B in crystal form II adopts an "open" conformation and is thus in the inactive form. In addition, we have determined the structures of two NS5B polymerase/non-nucleoside inhibitor complexes. Both inhibitors bind at a common binding site, which is nearly 35 A away from the polymerase active site and is located in the thumb domain. The binding pocket is predominantly hydrophobic in nature, and the enzyme inhibitor complexes are stabilized by hydrogen bonding and van der Waals interactions. Inhibitors can only be soaked in crystal form I and not in form II; examination of the enzyme-inhibitor complex reveals that the enzyme has undergone a dramatic conformational change from the form I (active) complex to the form II (inactive).

HCV NS5B polymerase-bound conformation of a soluble sulfonamide inhibitor by 2D transferred NOESY.

HCV NS5B RNA-dependent RNA polymerase (NS5B) is essential for viral replication and is therefore considered a target for antiviral drug development. From our ongoing screening effort in the search for new anti-HCV agents, a novel inhibitor 1 with low microM activity against the HCV NS5B polymerase was identified. SAR analysis indicated the optimal substitution pattern required for activity, for example, carboxylic acid group at 2-position of thiophene ring. We describe the steps taken to identify and solve the bioactive conformation of derivative 6 through the use of the transferred NOE method (trNOE).

Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCV NS5B polymerase and HCV subgenomic RNA replication. Part 1: Sulfonamides.

The discovery of a novel class of HCV NS5B polymerase inhibitors, 3-arylsulfonylamino-5-phenyl-thiophene-2-carboxylic acids is described. SAR studies have yielded several potent inhibitors of HCV polymerase as well as of HCV subgenomic RNA replication in Huh-7 cells.

Discovery of thiophene-2-carboxylic acids as potent inhibitors of HCV NS5B polymerase and HCV subgenomic RNA replication. Part 2: tertiary amides.

Further SAR studies on the thiophene-2-carboxylic acids are reported. These studies led to the identification of a series of tertiary amides that show inhibition of both HCV NS5B polymerase in vitro and HCV subgenomic RNA replication in Huh-7 cells. Structural insights about the bioactive conformation of this class of molecules were deduced from a combination of modeling and transferred NOE (trNOE) studies.

Adjunctive commissure splint therapy: a revised approach.

The management of trauma to the commissures has been an ongoing challenge for the medical and dental professions. Multiple surgical and prosthetic approaches have been used. Commissure splint therapy is often effective in association with surgery in reducing the effects of scar contraction that ultimately results in microstomia and reduced quality of life. This article describes methods of fabrication of the commissure splint appliance, the rationale for its modification, advantages, and disadvantages.

Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition.

X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0 and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on the protein, approximately 35 A from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen atoms of a carboxylate group on the inhibitor and two main chain amide nitrogen atoms of Ser(476) and Tyr(477) on NS5B. The inhibitor-binding site lies at the base of the thumb domain, near its interface with the C-terminal extension of NS5B. The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase.

Dental follow-up compliance in a population of irradiated head and neck cancer patients.

OBJECTIVE: This study assessed post-radiation therapy dental follow-up compliance in a population of head and neck cancer patients. STUDY DESIGN: A total of 334 dental charts were retrospectively reviewed to determine the follow-up status of dentate patients. All patients were informed of the importance of returning, after completing radiotherapy, for regular follow-up dental examinations on an indefinite basis. Data regarding compliance with these follow-up instructions over time were obtained. RESULTS: Approximately 170 (51%) of the 334 dentate patients were identified as being lost to dental follow-up. The mean point in time at which follow-up failure occurred was 7.5 months after the initial preirradiation dental examination. CONCLUSION: Dental follow-up compliance may be poor in this irradiated patient population, with follow-up failures potentially occurring less than 1 year after the completion of radiotherapy. Preradiation dental care planning must take into account the likelihood of patients being lost to follow-up.

The role of phenolic compounds and nutrients in determining food preference in greater snow geese.

We tested Buchsbaum's hypothesis that food palatability in geese is determined by a hierarchy of feeding cues among which deterrent secondary metabolites (mostly phenols) have a primary role (Buchsbaum et al. 1984). In preference tests, greater snow goose feeding was slightly depressed when grass was sprayed with ferulic acid but not when grass was sprayed with p-coumaric and tannic acids. Extracts of Timothy grass, red clover or alfalfa sprayed on grass also failed to depress goose feeding. In a multifactor experiment, phenol and protein content and height of grass were manipulated simultaneously. When ferulic acid was sprayed, protein and phenol content interacted in determining goose feeding preferences; protein content had no effect in the absence of phenol but did have an effect when phenol was added. When tannic acid was used in a similar experiment, results were inconclusive because of a significant and complex interaction between protein content and height of grass. Our results generally failed to support Buchsbaum's hypothesis that phenol content of plants has a primary role in determining food preference in geese. Protein content of plants seemed to be a more important factor.