Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen.

OBJECTIVES: Dalbavancin is a long-acting lipoglycopeptide with activity against gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA). The potential for lipoglycopeptides, with half-lives greater than 1 week, to select for resistance is unknown. Here we explore a case of MRSA central line-associated bloodstream infection in which dalbavancin and vancomycin non-susceptibility emerged in a urine isolate collected after the patient was treated with vancomycin and dalbavancin sequentially. METHODS: Isolates from blood and urine underwent susceptibility testing, and whole genome sequencing (WGS). The blood isolate was subjected to successive passage in vitro in the presence of escalating dalbavancin concentrations and the emergent isolate was subjected to repeat susceptibility testing and WGS. RESULTS: The blood isolate was fully susceptible to vancomycin; however, MICs of the urine isolate to dalbavancin, vancomycin, telavancin, and daptomycin were at least fourfold higher than the blood-derived strain. Both strains were indistinguishable by spa and variable number tandem repeat (VNTR) typing, and WGS revealed only seven variants, indicating clonality. Four variants affected genes, including a 3bp in-frame deletion in yvqF, a gene which has been implicated in glycopeptide resistance. Vancomycin and dalbavancin non-susceptibility emerged in the blood isolate after successive passage in vitro in the presence of dalbavancin, and WGS identified a single non-synonymous variant in yvqF. CONCLUSIONS: This is the first case in which VISA has emerged in the context of a dalbavancin-containing regimen. The selection for cross-resistance to vancomycin in vitro by dalbavancin exposure alone is troubling. Clinicians should be aware of the possibility for emergence of dalbavancin non-susceptibility and glycopeptide cross-resistance arising following therapy.

User involvement in the planning and delivery of mental health services: a cross-sectional survey of service users and providers.

OBJECTIVE: To identify methods for involving service users in the planning and delivery of psychiatric services and factors which may assist and impede this process. METHOD: A cross-sectional postal survey of user groups and providers of psychiatric services throughout Greater London (UK). RESULTS: Seventeen (94%) service providers and 29 (48%) user groups responded to the survey. Service providers employed a wide variety of different methods for involving users but none met national standards for user involvement (UI). Service providers stated that the main obstacle to UI was that users who took part were not representative of local patients. User groups highlighted staff resistance as a major obstacle and 80% stated that they were not satisfied with current arrangements for UI. CONCLUSION: While users and providers of mental health services were able to identify changes resulting from UI the responsiveness of staff and the representativeness of service users may be impeding this process.

Purification, crystallization and preliminary X-ray diffraction data from selenomethionine glycinamide ribonucleotide synthetase.

In this study, the overexpression, purification and crystallization of selenomethionine (SeMet) incorporated glycinamide ribonucleotide synthetase (GAR-syn) from Escherichia coli are reported. The overexpression of SeMet GAR-syn was placed under the control of the isopropylthio-beta-galactoside (IPTG) inducible T7 RNA-polymerase system. The newly developed construct contained a removable histidine tag on the amino terminus of GAR-syn, which allowed rapid purification using metal-chelate chromatography techniques. The SeMet GAR-syn crystals were grown by hanging-drop vapor diffusion and belong to the space group P212121 with unit-cell parameters a = 56.2, b = 62.4 and c = 129.8 A and a single monomer in the asymmetric unit. The crystals diffract to 1.6 A resolution and have led to the determination of multiple-wavelength anomalous diffraction phases to 2.2 A resolution.

Effectiveness of medical nutrition therapy provided by dietitians in the management of non-insulin-dependent diabetes mellitus: a randomized, controlled clinical trial.

OBJECTIVE: To assess the effect of medical nutrition therapy (MNT) provided by dietitians on medical and clinical outcomes for adults with non-insulin-dependent diabetes mellitus (NIDDM), and to compare MNT administered according to practice guidelines nutrition care (PGC) to MNT administered with basic nutrition care (BC). DESIGN: A prospective, randomized, controlled clinical trial of two levels of MNT on metabolic control in persons newly diagnosed with or currently under treatment for NIDDM was conducted at diabetes centers in three states (Minnesota, Florida, and Colorado). BC consisted of a single visit with a dietitian; PGC involved an initial visit with a dietitian followed by two visits during the first 6 weeks of the study period. Data were collected at entry to the study and at 3 and 6 months. SUBJECTS: Results are reported for 179 men and women aged 38 to 76 years: 85 assigned randomly to BC and 94 to PGC. This represents 72% of the 247 subjects enrolled. An additional 62 adults with NIDDM at one site who had no contact with a dietitian were identified as a nonrandom comparison group. OUTCOMES: Medical outcome measures included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and serum lipid levels. Clinical outcomes included weight, body mass index, waist-to-hip ratio, and changes in medical therapy. STATISTICAL ANALYSES: Initial analysis of the discrete variables was done using the chi 2 statistic with Yates' correction. Initial analysis of continuous variables was done by analysis of variance. The changes in variables between time periods were analyzed by paired t test, and comparisons between groups were analyzed using a t test for independent groups. RESULTS: At 6 months, PGC resulted in significant improvements in blood glucose control as indicated by FPG and HbA1c levels and BC resulted in significant improvements in HbA1c level. Participants assigned to the PGC group had a mean FPG level at 6 months that was 10.5% lower than the level at entry, and those in the BC group had a 5.3% lower value. Among subjects who had diabetes for longer than 6 months, those who received PGC had a significantly better HbA1c level at 3 months compared with those receiving BC. The comparison group showed no improvement in glycemic control over a comparable 6 months. PGC subjects had significant improvements in cholesterol values at 6 months, and subjects in both the PGC and the BC groups had significant weight loss. CONCLUSIONS: MNT provided by dietitians resulted in significant improvements in medical and clinical outcomes in both the BC and PGC groups and is beneficial to persons with NIDDM. Persons with a duration of diabetes longer than 6 months tended to do better with PGC than with BC. Because of the upward trend in glucose levels after 3 months, ongoing MNT by dietitians is important for long-term metabolic control.

Cost-effectiveness of medical nutrition therapy provided by dietitians for persons with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To conduct a cost analysis and cost-effectiveness study based on a randomized clinical trial of basic nutrition care (BC) and practice guidelines nutrition care (PGC) provided by dietitians in outpatient clinics. DESIGN: Subjects with non-insulin-dependent diabetes mellitus (NIDDM) from three states (Minnesota, Florida, Colorado) were randomly assigned to a group receiving BC or a group receiving PGC for a 6-month clinical trial. Along with data about medical and clinical outcomes, data about cost resources were collected. The cost-effectiveness of PGC compared with BC was calculated using per-patient costs and glycemic outcomes for the 6 months of the study. A net cost-effectiveness ratio comparing BC and PGC, including the cost savings resulting from changes in medical therapy, was also calculated. SUBJECTS: The study reports on a sample of 179 subjects with NIDDM between the ages of 38 and 76 years who completed the clinical trial. RESULTS: Patients in the PGC group experienced a mean 1.1 +/- 2.8 mmol/L decrease in fasting plasma glucose level 6 months after entry to the study, for a total per-patient cost of $112. PGC costs included one glycated hemoglobin assay used by the dietitian to evaluate nutrition outcomes. Patients in the BC group experienced a mean 0.4 +/- 2.7 mmol/L decrease, for a total per-patient cost of $42. In the PGC group, 17 persons had changes in therapy, which yielded an average 12-month cost savings prorated for all patients of $31.49. In contrast, in the BC group, 9 persons had changes in therapy, for an average 12-month prorated cost savings of $3.13. Each unit of change in fasting plasma glucose level from entry to the 6-month follow-up can be achieved with an investment of $5.75 by implementing BC or of $5.84 by implementing PGC. If net costs are considered (per-patient costs--cost savings due to therapy changes), the cost-effectiveness ratios become $5.32 for BC and $4.20 for PGC, assuming the medical changes in therapy were maintained for 12 months. APPLICATIONS: These findings suggest that individualized nutrition interventions can be delivered by experienced dietitians with a reasonable investment of resources. Cost-effectiveness is enhanced when dietitians are engaged in active decision making about intervention alternatives based on the patient's needs.

Practice guidelines for medical nutrition therapy provided by dietitians for persons with non-insulin-dependent diabetes mellitus. International Diabetes Center.

Nutrition practice guidelines define a systematic approach for medical nutrition therapy (MNT) provided by dietitians and are derived from scientific evidence and expert opinion. Nutrition practice guidelines for persons with non-insulin-dependent diabetes mellitus (NIDDM) can be implemented for those with newly diagnosed or previously diagnosed NIDDM at the first visit to a dietitian for initial or ongoing MNT. The guidelines apply to patients treated with MNT alone, MNT and oral glucose-lowering agents, or MNT and insulin. They provide a framework to assist the dietitian in the assessment, intervention (nutrition prescription, education, goal setting), and evaluation of outcomes for MNT. Minimum referral data for clinical decision making and outcome criteria are defined. Basic nutrition care is defined as one visit with the dietitian. Nutrition practice guidelines care consists of a series of visits with the dietitian. At the second follow-up visit, the dietitian assesses what has been accomplished with the nutrition interventions. If the patient has implemented the nutrition recommendations to the best of his or her ability and has not achieved the treatment goals, the dietitian should notify the physician and recommend that changes in medical management are needed. Ongoing nutrition care is recommended at 6-month to 1-year intervals for both basic and practice guidelines care.

Characterization of a rat cDNA clone encoding calcium/calmodulin-dependent protein kinase I.

Two cDNA clones encoding calcium/calmodulin-dependent (CaM) protein kinase I were isolated. In contrast to the previously reported CaM kinase I cDNA, which encodes a protein with a mass of 37 kDa, the clones identified in this study encode a protein (10-1/CaM kinase I) with a predicted mass of 42 kDa; the size of 10-1/CaM kinase I was verified by hybrid-selected translation.

Medial frontal lesions, postoperative treatment with an ACTH(4-9) analog, and acquisition of a win-shift spatial strategy.

Forty adult rats of both genders were randomly assigned to one of four factorial groups and prepared with either medial frontal or sham lesions. On the day of surgery osmotic mini-pumps that had been prepared to deliver either 12.5 micrograms of ACTH(4-9) analog per 24 h or saline for the next 14 days were installed in a subcutaneous location. One month following surgery, these animals were studied in an avoidance conditioning experiment. Four to 6 months later their abilities to learn a water maze win-shift spatial strategy was investigated. The brain-damaged rats were found to be deficient on all behavioral measures examined: errors to criterion, days to criterion, and perseverative errors. Although post-neurosurgical administration of the ACTH 4-9 analog has been shown to improve behavioral recovery from brain damage in some studies, the peptide failed to improve the behaviors examined here.