Caring for Caregivers: An Evaluation of Schwartz Rounds in a Paediatric Setting

Aim To evaluate the views of staff on a multidisciplinary intervention for promoting reflective practice called Schwartz Rounds. Methods The data was collected via an anonymous, opt-in standard feedback form filled in by attendees of Schwartz rounds immediately after they had attended a round. The form contained statements that could be rated using a Likert scale. The rounds were open to all staff in Temple Street Children's University Hospital (TSCUH). The data was quantitatively analysed using SPSS software. A thematic analysis of the free text comments from the standard feedback form was also performed. Results In 95% (n=189) of the returned forms, the statements were all rated positively. A Kruskal-Wallis test (p= .466) showed there was no significant difference between clinical and non-clinical staff in terms of how much they agreed to the statements about the rounds. Conclusion The results showed that there was a positive perception of Schwartz rounds in TSCUH.

Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels.

UNLABELLED: The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: (1) nanofillers influence neurite extension and (2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10-100-µg/mL) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-µg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. STATEMENT OF SIGNIFICANCE: Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon nanotubes and other novel materials are being explored for novel nano-neuro devices based on their unique properties. Neuronal growth on carbon nanotubes has been studied in 2D since the early 2000s demonstrating increased outgrowth, synapse formation and network activity. In this work, single-walled carbon nanotubes were selected as one possible electrically-conductive material, dispersed within a 3D hydrogel containing primary neurons; extending previous 2D work to 3D to evaluate outgrowth within nanomaterial composites with electrical stimulation. This is the first study to our knowledge that stimulates neurons in 3D composite nanomaterial-laden hydrogels. Examination of electrically conductive biomaterials may serve to promote regrowth following injury or in long term stimulation.

A Primitive Growth Factor, NME7AB , Is Sufficient to Induce Stable Naïve State Human Pluripotency; Reprogramming in This Novel Growth Factor Confers Superior Differentiation.

Scientists have generated human stem cells that in some respects mimic mouse naïve cells, but their dependence on the addition of several extrinsic agents, and their propensity to develop abnormal karyotype calls into question their resemblance to a naturally occurring "naïve" state in humans. Here, we report that a recombinant, truncated human NME7, referred to as NME7AB here, induces a stable naïve-like state in human embryonic stem cells and induced pluripotent stem cells without the use of inhibitors, transgenes, leukemia inhibitory factor (LIF), fibroblast growth factor 2 (FGF2), feeder cells, or their conditioned media. Evidence of a naïve state includes reactivation of the second X chromosome in female source cells, increased expression of naïve markers and decreased expression of primed state markers, ability to be clonally expanded and increased differentiation potential. RNA-seq analysis shows vast differences between the parent FGF2 grown, primed state cells, and NME7AB converted cells, but similarities to altered gene expression patterns reported by others generating naïve-like stem cells via the use of biochemical inhibitors. Experiments presented here, in combination with our previous work, suggest a mechanistic model of how human stem cells regulate self-replication: an early naïve state driven by NME7, which cannot itself limit self-replication and a later naïve state regulated by NME1, which limits self-replication when its multimerization state shifts from the active dimer to the inactive hexamer.

Predicting adult weight change in the real world: a systematic review and meta-analysis accounting for compensatory changes in energy intake or expenditure.

BACKGROUND: Public health and clinical interventions for obesity in free-living adults may be diminished by individual compensation for the intervention. Approaches to predict weight outcomes do not account for all mechanisms of compensation, so they are not well suited to predict outcomes in free-living adults. Our objective was to quantify the range of compensation in energy intake or expenditure observed in human randomized controlled trials (RCTs). METHODS: We searched multiple databases (PubMed, CINAHL, SCOPUS, Cochrane, ProQuest, PsycInfo) up to 1 August 2012 for RCTs evaluating the effect of dietary and/or physical activity interventions on body weight/composition. INCLUSION CRITERIA: subjects per treatment arm ≥5; ≥1 week intervention; a reported outcome of body weight/body composition; the intervention was either a prescribed amount of over- or underfeeding and/or supervised or monitored physical activity was prescribed; ≥80% compliance; and an objective method was used to verify compliance with the intervention (for example, observation and electronic monitoring). Data were independently extracted and analyzed by multiple reviewers with consensus reached by discussion. We compared observed weight change with predicted weight change using two models that predict weight change accounting only for metabolic compensation. FINDINGS: Twenty-eight studies met inclusion criteria. Overfeeding studies indicate 96% less weight gain than expected if no compensation occurred. Dietary restriction and exercise studies may result in up to 12-44% and 55-64% less weight loss than expected, respectively, under an assumption of no behavioral compensation. INTERPRETATION: Compensation is substantial even in high-compliance conditions, resulting in far less weight change than would be expected. The simple algorithm we report allows for more realistic predictions of intervention effects in free-living populations by accounting for the significant compensation that occurs.

Will reducing sugar-sweetened beverage consumption reduce obesity? Evidence supporting conjecture is strong, but evidence when testing effect is weak.

We provide arguments to the debate question and update a previous meta-analysis with recently published studies on effects of sugar-sweetened beverages (SSBs) on body weight/composition indices (BWIs). We abstracted data from randomized controlled trials examining effects of consumption of SSBs on BWIs. Six new studies met these criteria: (i) human trials, (ii) ≥ 3 weeks duration, (iii) random assignment to conditions differing only in consumption of SSBs and (iv) including a BWI outcome. Updated meta-analysis of a total of seven studies that added SSBs to persons' diets showed dose-dependent increases in weight. Updated meta-analysis of eight studies attempting to reduce SSB consumption showed an equivocal effect on BWIs in all randomized subjects. When limited to subjects overweight at baseline, meta-analysis showed a significant effect of roughly 0.25 standard deviations (more weight loss/less weight gain) relative to controls. Evidence to date is equivocal in showing that decreasing SSB consumption will reduce the prevalence of obesity. Although new evidence suggests that an effect may yet be demonstrable in some populations, the integrated effect size estimate remains very small and of equivocal statistical significance. Problems in this research area and suggestions for future research are highlighted.

Acute bacterial maxillary sinusitis: time to symptom resolution and return to normal activities with moxifloxacin.

OBJECTIVES: This prospective, single-arm, open-label, multicentre phase IV (postmarketing surveillance) study determined time to resolution of key symptoms and return to normal activities in adults with acute bacterial maxillary sinusitis treated with moxifloxacin 400 mg qd for 10 days. The study also assessed whether responses to the Sino-Nasal Outcome Test-16 (SNOT-16) questionnaire [not yet validated for acute bacterial sinusitis (ABS)] accurately reflect clinical findings in these patients. METHODS: Adults with a clinical diagnosis of acute bacterial maxillary sinusitis with signs/symptoms present for > or = 7 but < 28 days took part. Patients were evaluated bacteriologically and clinically on day 1 (pretherapy), days 2-4 and 10-13 (test of cure), for bacterial presence and improvement/resolution of the signs/symptoms of acute bacterial maxillary sinusitis. They completed SNOT-16 and Activity Impairment Assessment questionnaires daily, before receiving moxifloxacin, until day 10. RESULTS: In both the bacteriologically and clinically evaluable populations, over 85% of patients showed clinical improvement by day 2, rising to over 96% by day 4. Pretherapy, according to the SNOT-16 questionnaire, almost all of the bacteriologically evaluable patients reported facial pain/pressure but this proportion had fallen to below 50% by day 4. In the bacteriologically evaluable population, 32/42 (76%) patients reported an improvement in facial pain/pressure from the pretherapy visit to day 4. Of patients showing improvement, 50% improved from 'moderate-to-severe facial pain' at pretherapy to 'no problem' at day 4. At day 4, 45-50% of patients reported impairment of normal activities, compared with 79-88% pretherapy. CONCLUSIONS: Moxifloxacin rapidly improves the signs and symptoms of acute bacterial maxillary sinusitis and results in clinical cure in most patients. Responses to the SNOT-16 questionnaire accurately reflected clinical assessments, indicating that when fully validated the SNOT-16 questionnaire may be a valuable tool for the assessment of patient outcomes in ABS.

Differences in physician and patient perceptions of uncomplicated UTI symptom severity: understanding the communication gap.

Uncomplicated urinary tract infection (uUTI) is the most common bacterial infection encountered in clinical practice but evaluation and treatment of the illness vary considerably among physicians. The literature suggests that there is often a gap in the perception of symptom severity between physician and patient, a gap that may be a result of the different models they use to explain and manage disease, a result of misinformation or misconceptions about uUTIs, or a result of poor patient-physician communication. This gap in perceptions about uUTI may lead to poor patient care, decreased quality of life and increased antibiotic resistance. Good communication between patient and physician has been shown to result in improved health outcomes. Several approaches to improving communication during consultations have been described in the literature. Physician and patient education and their agreement about any disease, including uUTI can be expected to improve treatment compliance and reduce the incidence of recurrence of such infections. Future work should focus on improvement of communication during clinical consultations to encourage appropriate bidirectional sharing of clinical and patient information. Further research about behavioural risk factors for uUTI may allow evidence-based information to be used in educational programmes.

Relationship of solution and protein-bound structures of DNA duplexes with the major intrastrand cross-link lesions formed on cisplatin binding to DNA.

DNA bases in the three-base-pair (3bp) region of duplexes with the two major lesions of cisplatin (cis-PtCl(2)(NH(3))(2)) with DNA, namely d(XGG) and d(XAG) ( = N7-platinated base), differ in their relative positions by as much as approximately 3.5 A in structures in the literature. Such large differences impede drug design and assessments of the effects of protein binding on DNA structure. One recent and several past structures based on NMR-restrained molecular dynamics (RMD) differ significantly from the reported X-ray structure of an HMG-bound XGG 16-mer DNA duplex (Ohndorf, U.-M.; Rould, M. A.; He, Q.; Pabo, C. O.; Lippard, S. J. Nature 1999, 399, 708). This 16-mer structure has several significant novel and unique features (e.g., a bp step with large positive shift and slide). Hypothesizing that novel structural features in the XGG or XAG region of duplexes elude discovery by NMR methods (especially because of the flexible nature of the 3bp region), we studied an oligomer with only G.C bp's in the XGGY site by NMR methods for the first time. This 9-mer gave a 5'-G N1H signal with a normal shift and intensity and showed clear NOE cross-peaks to C NHb and NHe. We assigned for the first time (13)C NMR signals of a duplex with a GG lesion. These data, by adding NMR-based criteria to those inherent in NOESY and COSY data, have more specifically defined the structural features that should be present in an acceptable model. In particular, our data indicated that the sugar of the X residue has an N pucker and that the GG cross-link should have a structure similar to the original X-ray structure of cis-Pt(NH(3))(2)(d(pGpG)) (Sherman S. E.; Gibson, D.; Wang, A. H.-J.; Lippard, S. J. J. Am. Chem. Soc. 1988, 110, 7368). With these restrictions added to NOE restraints, an acceptable model was obtained only when we started our modeling with the 16-mer structural features. The new X-ray/NMR-based model accounted for the NOESY data better than NOE-based models, was very similar in structure to the 16-mer, and differed from solely NOE-based models. We conclude that all XGG and XAG (X = C or T) duplexes undoubtedly have structures similar to those of the 16-mer and our model. Thus, protein binding does not change greatly the structure of the 3bp region. The structure of this region can now be used in understanding structure-activity relationships needed in the design of new carrier ligands for improving Pt anticancer drug activity.

Transcriptional downregulation of ATM by EGF is defective in ataxia-telangiectasia cells expressing mutant protein.

There is evidence that ATM plays a wider role in intracellular signalling in addition to DNA damage recognition and cell cycle control. In this report we show that activation of the EGF receptor is defective in ataxia-telangiectasia (A-T) cells and that sustained stimulation of cells with EGF downregulates ATM protein in control cells but not in A-T cells expressing mutant protein. Concomitant with the downregulation of ATM, DNA-binding activity of the transcription factor Sp1 decreased in controls after EGF treatment but increased from a lower basal level in A-T cells to that in untreated control cells. Mutation in two Sp1 consensus sequences in the ATM promoter reduced markedly the capacity of the promoter to support luciferase activity in a reporter assay. Overexpression of anti-sense ATM cDNA in control cells decreased the basal level of Sp1, which in turn was increased by subsequent treatment of cells with EGF, similar to that observed in A-T cells. On the other hand full-length ATM cDNA increased the basal level of Sp1 binding in A-T cells, and in response to EGF Sp1 binding decreased, confirming that this is an ATM-dependent process. Contrary to that observed in control cells there was no radiation-induced change in ATM protein in EGF-treated A-T cells and likewise no alteration in Sp1 binding activity. The results demonstrate that EGF-induced downregulation of ATM (mutant) protein in A-T cells is defective and this appears to be due to less efficient EGFR activation and abnormal Sp1 regulation.

Rapid radiation-induction of ATM protein levels in situ.

Ataxia-telangiectasia (A-T) is characterised by hypersensitivity to ionising radiation (IR), immunodeficiency, neurodegeneration and predisposition to malignancy. Mutations in the A-T gene (ATM) often result in reduced levels of ATM protein and/or compromise ATM function. IR induced DNA damage is known to rapidly upregulate ATM kinase activity/phosphorylation events in the control of cell cycle progression and other processes. Variable expression of ATM levels in different tissues and its upregulation during cellular proliferation indicate that the level of ATM is also regulated by mechanisms other than gene mutation. Here, we report on the IR induction of ATM protein levels within a number of different cell types and tissues. Induction had begun within 5 min and peaked within 2 h of exposure to 2 Gy of IR, suggesting a rapid post-translational mechanism. Low basal levels of ATM protein were more responsive to IR induction compared to high ATM levels in the same cell type. Irradiation of fresh skin biopsies led to an average three-fold increase in ATM levels while immunohistochemical analyses indicated "low expressing" cells within the basal layer with ten-fold increases in ATM levels following IR. ATM "high expressing" lymphoblastoid cell lines (LCLs) which were initially resistant to the radiation-induction of ATM levels also became responsive to IR after ATM antisense expression was used to reduce the basal levels of the protein. These results demonstrate that ATM is present in variable amounts in different tissue/cell types and where basal levels are low ATM levels can be rapidly induced by IR to saturable levels specific for different cell types. ATM radiation-induction is a sensitive and rapid radioprotective response that complements the IR mediated activation of ATM.

Epidermal growth factor sensitizes cells to ionizing radiation by down-regulating protein mutated in ataxia-telangiectasia.

Epidermal growth factor (EGF) has been reported to either sensitize or protect cells against ionizing radiation. We report here that EGF increases radiosensitivity in both human fibroblasts and lymphoblasts and down-regulates both ATM (mutated in ataxia-telangiectasia (A-T)) and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). No further radiosensitization was observed in A-T cells after pretreatment with EGF. The down-regulation of ATM occurs at the transcriptional level. Concomitant with the down-regulation of ATM, the DNA binding activity of the transcription factor Sp1 decreased. A causal relationship was established between these observations by demonstrating that up-regulation of Sp1 DNA binding activity by granulocyte/macrophage colony-stimulating factor rapidly reversed the EGF-induced decrease in ATM protein and restored radiosensitivity to normal levels. Failure to radiosensitize EGF-treated cells to the same extent as observed for A-T cells can be explained by induction of ATM protein and kinase activity with time post-irradiation. Although ionizing radiation damage to DNA rapidly activates ATM kinase and cell cycle checkpoints, we have provided evidence for the first time that alteration in the amount of ATM protein occurs in response to both EGF and radiation exposure. Taken together these data support complex control of ATM function that has important repercussions for targeting ATM to improve radiotherapeutic benefit.

Development and use of a virtual NMR facility.

We have developed a "virtual NMR facility" (VNMRF) to enhance access to the NMR spectrometers in Pacific Northwest National Laboratory's Environmental Molecular Sciences Laboratory (EMSL). We use the term virtual facility to describe a real NMR facility made accessible via the Internet. The VNMRF combines secure remote operation of the EMSL's NMR spectrometers over the Internet with real-time videoconferencing, remotely controlled laboratory cameras, real-time computer display sharing, a Web-based electronic laboratory notebook, and other capabilities. Remote VNMRF users can see and converse with EMSL researchers, directly and securely control the EMSL spectrometers, and collaboratively analyze results. A customized Electronic Laboratory Notebook allows interactive Web-based access to group notes, experimental parameters, proposed molecular structures, and other aspects of a research project. This paper describes our experience developing a VNMRF and details the specific capabilities available through the EMSL VNMRF. We show how the VNMRF has evolved during a test project and present an evaluation of its impact in the EMSL and its potential as a model for other scientific facilities. All Collaboratory software used in the VNMRF is freely available from www.emsl.pnl.gov:2080/docs/collab.

Counseling youth in tobacco-use prevention: determinants of clinician compliance.

OBJECTIVE: The rate and determinants of tobacco prevention and cessation counseling to youth were examined for orthodontists participating in a controlled trial to decrease the incidence of tobacco use among adolescents. METHODS: A cross-sectional interview design in private practice offices throughout Southern California was used. The survey was completed with 126 (82%) orthodontists. Clinicians randomly assigned to the experimental group (N = 77) received a 1.5 h workshop, anti-tobacco materials, reimbursement for provision of anti-tobacco prescriptions, and quarterly checkup visits. Control group clinicians (N = 77) did not receive training, materials, or visits. RESULTS: Experimental group clinicians talked to more adolescent nonsmokers about never beginning tobacco use than did control group clinicians (P < 0.05). Experimental group clinicians talked to more adolescent tobacco users than did control group clinicians; however, the difference was not statistically significant. Content and determinants of counseling were affected by participation in the intervention. CONCLUSIONS: Though training and support increased prevention and cessation counseling, absolute rates remained less than optimal. Social learning factors were associated with prevention and cessation counseling.

Identification of Resistance to Thielaviopsis basicola in Diploid Cotton.

A screening program to find sources of resistance to Thielaviopsis basicola in cotton identified a diploid cotton (Gossypium arboreum, PI 1415) with apparent high resistance to this pathogen. Seedlings were obtained from self-pollinated seed taken from the resistant plant (PI 1415) and grown in growth chamber tests with the cultivars (tetraploid G. hirsutum) Paymaster HS-26 and Paymaster Tejas as controls. Seedlings were grown for 20 days in naturally infested field soil and evaluated for root growth and root necrosis. In all tests, PI 1415 had less (P = 0.001) root necrosis than the cultivars HS-26 and Tejas. A triadimenol seed treatment also resulted in less (P = 0.001) root necrosis for all three cotton genotypes, and the response was additive with level of disease resistance. Incorporation of the resistance factor from PI 1415 into tetraploid upland cotton may greatly reduce damage by black root rot, especially in combination with fungicide seed treatments.

Application of proteases to the identification of chiral modifications in synthetic peptides.

Racemization of amino acids during solid-phase synthesis of peptides leads to the formation of side products that are chirally modified peptides. The chiral specificity of enzymes can be exploited to identify the sites of the modifications in these impurities. One such impurity, designated X5, was isolated from the target peptide, Fel-1, and demonstrated to be an optical isomer of Fel-1 by N-terminal sequencing and mass spectrometry. A chymotryptic digest was done on the isolated X5 and Fel-1. The fragments were separated on reversed-phase high-performance liquid chromatography (HPLC). Mass spectral data on the fragment from X5, with a different retention time from the analogous fragment of Fel-1, suggested that the modification was in the N-terminal portion of the peptide. Enzymatic digestion by Asp-N protease followed by HPLC of the fragments and mass spectral analysis provided evidence that an aspartic acid at position 5 was a D-amino acid in X5, because that position was not cleaved. These results contributed to the identification of X5 as an optical isomer of Fel-1, with a D-aspartic acid replacing an L-aspartic acid normally present at position 5.

ATM associates with and phosphorylates p53: mapping the region of interaction.

The human genetic disorder ataxia-telangiectasia (AT) is characterized by immunodeficiency, progressive cerebellar ataxia, radiosensitivity, cell cycle checkpoint defects and cancer predisposition. The gene mutated in this syndrome, ATM (for AT mutated), encodes a protein containing a phosphatidyl-inositol 3-kinase (PI-3 kinase)-like domain. ATM also contains a proline-rich region and a leucine zipper, both of which implicate this protein in signal transduction. The proline-rich region has been shown to bind to the SH3 domain of c-Abl, which facilitates its phosphorylation and activation by ATM. Previous results have demonstrated that AT cells are defective in the G1/S checkpoint activated after radiation damage and that this defect is attributable to a defective p53 signal transduction pathway. We report here direct interaction between ATM and p53 involving two regions in ATM, one at the amino terminus and the other at the carboxy terminus, corresponding to the PI-3 kinase domain. Recombinant ATM protein phosphorylates p53 on serine 15 near the N terminus. Furthermore, ectopic expression of ATM in AT cells restores normal ionizing radiation (IR)-induced phosphorylation of p53, whereas expression of ATM antisense RNA in control cells abrogates the rapid IR-induced phosphorylation of p53 on serine 15. These results demonstrate that ATM can bind p53 directly and is responsible for its serine 15 phosphorylation, thereby contributing to the activation and stabilization of p53 during the IR-induced DNA damage response.

Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia.

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscular blocking agents. To date, eight mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and have identified a G to T transition mutation which results in the replacement of a conserved arginine (Arg) at position 614 with a leucine (Leu). The Arg614Leu mutation was present in three unrelated MHS individuals of 151 investigated. The mutation was not detected in 148 normal chromosomes and segregated precisely with MHS in family members from one of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mutation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cys probands is presented.

Tracking and follow-up of 16,915 adolescents: minimizing attrition bias.

This paper reports a multi-dimensional approach to minimize drop-outs from a two-year follow-up of a clinical trial designed to reduce initiation of tobacco use in 16,915 adolescent orthodontic patients. A hierarchical approach to data collection and tracking was employed. Seventy percent of participants were reached and interviewed at home by telephone. Strategies used to survey remaining participants included calling parents' work numbers and directory assistance, reviewing orthodontists' charts, sending surveys by mail, offering incentives, and using reverse telephone directories. More than 92% of the participants completed follow-up surveys. Multivariate analyses showed that baseline tobacco and alcohol use predicted loss to follow-up. Similarly, the number of procedures used to track each participant predicted presence of risk behaviors at post-test, demonstrating that an organized tracking hierarchy curtailed even greater compromises to internal and external validity. Evaluation and costs of individual strategies are discussed.

Detection of a novel mutation in the ryanodine receptor gene in an Irish malignant hyperthermia pedigree: correlation of the IVCT response with the affected and unaffected haplotypes.

Defects in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia (MH), an autosomal dominant disorder of skeletal muscle and one of the main causes of death resulting from anaesthesia. Susceptibility to MH (MHS) is determined by the level of tension generated in an in vitro muscle contracture test (IVCT) in response to caffeine and halothane. To date, mutation screening of the RYR1 gene in MH families has led to the identification of eight mutations. We describe here the identification of a novel mutation, Arg552Trp, in the RYR1 gene, which is clearly linked to the MHS phenotype in a large, well characterised Irish pedigree. Considering that the RYR1 protein functions as a tetramer, correlation of the IVCT with the affected and unaffected haplotypes was performed on the pedigree to investigate if the normal RYR1 allele in affected subjects contributes to the variation in the IVCT. The results show that the normal RYR1 allele is unlikely to play a role in IVCT variation.

Clinician compliance with primary prevention of tobacco use: the impact of social contingencies.

BACKGROUND: This study evaluated clinicians' compliance with delivering written advice and information against tobacco use (prevention prescriptions) to adolescent patients. METHODS: Clinicians in 77 orthodontic offices were trained (and asked) to provide anti-tobacco counseling and prescriptions to 10- to 18-year-olds for 2 years. Each of eight prescriptions was provided for distribution to adolescent patients. Information concerning prescription-tracking methods and operant learning theory variables such as modeling and feedback was obtained using a cross-sectional interview of clinical staff. The proportion of prescriptions written was regressed on possible "determinants." Analyses were replicated for two time periods. RESULTS: Mean anti-tobacco prescription compliance was 66 and 73% for two separate time periods. Multiple regression analyses were computed for the first (R = 0.45, F(7,63) = 2.29, P < 0.001) and second (R = 0.48, F(7,63) = 2.76, P < 0.001) time periods. Prescription tracking and praise from patients were significant correlates for the first time period; praise and modeling were significant for the second time period. Twenty and twenty-three percent, respectively, of the variance in office prescription rate was explained. CONCLUSIONS: Results suggest that compliance with primary prevention procedures may be influenced by feedback from patients, staff modeling, and formal office tracking information.