Infrared spectroscopy of the nitrogenase MoFe protein under electrochemical control: potential-triggered CO binding.

We demonstrate electrochemical control of the nitrogenase MoFe protein, in the absence of Fe protein or ATP, using europium(iii/ii) polyaminocarboxylate complexes as electron transfer mediators. This allows the potential dependence of proton reduction and inhibitor (CO) binding to the active site FeMo-cofactor to be established. Reduction of protons to H2 is catalyzed by the wild type MoFe protein and ß-98Tyr→His and ß-99Phe→His variants of the MoFe protein at potentials more negative than -800 mV (vs. SHE), with greater electrocatalytic proton reduction rates observed for the variants compared to the wild type protein. Electrocatalytic proton reduction is strongly attenuated by carbon monoxide (CO), and the potential-dependence of CO binding to the FeMo-cofactor is determined by in situ infrared (IR) spectroelectrochemistry. The vibrational wavenumbers for CO coordinated to the FeMo-cofactor are consistent with earlier IR studies on the MoFe protein with Fe protein/ATP as reductant showing that electrochemically generated states of the protein are closely related to states generated with the native Fe protein as electron donor.

Generating single metalloprotein crystals in well-defined redox states: electrochemical control combined with infrared imaging of a NiFe hydrogenase crystal.

We describe an approach to generating and verifying well-defined redox states in metalloprotein single crystals by combining electrochemical control with synchrotron infrared microspectroscopic imaging. For NiFe hydrogenase 1 from Escherichia coli we demonstrate fully reversible and uniform electrochemical reduction from the oxidised inactive to the fully reduced state, and temporally resolve steps during this reduction.

Developing the continuum of dental education: including dental foundation trainers in the delivery of a community-based clinical teaching programme.

INTRODUCTION: Despite advances in evidence-based dental school educational programmes, the charge is sometimes made that dental students are 'no longer as good as they used to be'. Recent modifications have meant that dental education is now a 'life-long experience', of which dental school is the initial, albeit very important, component. Contemporary dental students will normally enter dental foundation (DF) training on completion of dental school. As such there may be value in including DF trainers in dental school teaching programmes. The aim of this paper is to report the experiences, feedback and opinions of these DF trainers following their first-hand experience of the community-based clinical teaching programme at Cardiff, and assess if their perspectives of contemporary dental student education changed following this. MATERIALS AND METHODS: DF trainers were invited to attend the community-based clinical teaching programme at Cardiff on an observer basis. Twenty-four DF trainers attended, following which evaluation questionnaires were completed. Information sought included opinions and attitudes to the teaching programme, the physical environment in which the teaching programme took place, knowledge and attitudes towards community-based clinical teaching and modifications that DF trainers would make to the teaching programme to further improve the knowledge, skills and attributes of dental school graduates for DF training. RESULTS: Responses were received from 20 DF trainers (response rate = 83%). All 20 respondents felt that the teaching provided within the community-based clinical teaching programme was appropriate, with one respondent noting that it was like 'a day in the life of a dental practice', 'where anything could present'. Sixteen respondents were satisfied with the scope and content of the community-based clinical teaching programme, with a small number recommending inclusion of teaching in relation to inlays/onlays (n = 2), simple orthodontics (n = 1) and splinting (n = 1). Eighteen respondents reported that they felt students were adequately prepared for entry into DF training. All 20 respondents reported that their visit to the community-based clinical teaching programme had improved their perception of contemporary dental school education with one respondent noting: 'I am certainly more confident about students graduating' and another noting: 'It has reassured me that there are final year dental students that appear very professional and competent'. CONCLUSIONS: This investigation has demonstrated there is much to be gained by inclusion of DF trainers in undergraduate dental student community-based clinical teaching programmes. In an era where tensions exist between dental school teaching and subsequent DF training and independent practice, inclusion of DF trainers can exert positive pressures on dental school programmes and on DF training to ensure that young and newly graduating dentists are best prepared to meet the needs of their patients.

Preparing dental students for careers as independent dental professionals: clinical audit and community-based clinical teaching.

Community-based clinical teaching programmes are now an established feature of most UK dental school training programmes. Appropriately implemented, they enhance the educational achievements and competences achieved by dental students within the earlier part of their developing careers, while helping students to traverse the often-difficult transition between dental school and vocational/foundation training and independent practice. Dental school programmes have often been criticised for 'lagging behind' developments in general dental practice - an important example being the so-called 'business of dentistry', including clinical audit. As readers will be aware, clinical audit is an essential component of UK dental practice, with the aims of improving the quality of clinical care and optimising patient safety. The aim of this paper is to highlight how training in clinical audit has been successfully embedded in the community-based clinical teaching programme at Cardiff.

Evaluation of a community-based clinical teaching programme by current and former student dental therapists and dental hygienists: a pilot investigation.

AIM: There has been considerable expansion in the involvement of community-based clinical teaching programmes (sometimes termed 'outreach teaching') in UK and other international dental schools. While there has been much interest in the role of this educational methodology in the professional and educational development of student dentists, there has been little, if no, consideration of this form of teaching in relation to dental care professional (DCP) students. The aim of this pilot investigation was to report the feedback and evaluation of current and former student dental therapists and dental hygienists on their experience on the St David's community-based clinical teaching programme at Cardiff. METHODS: In Autumn 2009, a questionnaire was distributed by hand to the current second year student dental therapist and dental hygiene class at Cardiff (n = 18) and by post to the dental therapist and dental hygiene classes of 2004 (n = 16) and 2007 (n = 17). The questionnaire included both 'open' and 'closed' questions. RESULTS: Thirty responses were returned (response rate = 59%; 2004 (n = 5, 31%), 2007 (n = 9, 53%), current class (n = 16, 89%)). Seventy percent of respondents (n = 21) reported that they found the community-based clinical teaching programme to be a pleasant working environment and close to subsequent independent practice. Seventy-seven percent (n = 23) reported that their confidence performing nonsurgical periodontal treatment had increased while at the programme. One respondent commented that the programme was '...an invaluable and insightful introduction to what it would be like working in practice. Without being given the experience, it would have been a big shock to the system when I started working in practice...' CONCLUSION: This pilot investigation has revealed that current and former dental therapist and dental hygiene students are enthusiastic in their support for the inclusion of community-based clinical teaching programmes in their educational and professional development. Most former and current dental therapist and dental hygiene students noted the positive effects of this form of training on their subsequent clinical careers.

Outreach training: the special interest group's report.

Following three sessions at ADEE Annual Meetings, the special interest group on outreach training presents a brief report of its proceedings. Outreach, here, is clinical teaching away from the home dental school. After covering the diversity and benefits of programmes, the report considers different models and the relationship between contexts and outcomes. It concludes that: outreach provides access to additional resources; programmes prepare students for the demands of the profession; a programme's design should harmonise with both its context and its objectives; and, the educational benefits warrant the additional organisation involved.

Student perspectives and opinions on their experience at an undergraduate outreach dental teaching centre at Cardiff: a 5-year study.

AIM: Outreach teaching is now regarded as a desirable component of undergraduate dental teaching programmes in the UK. A purpose-built undergraduate dental outreach-training centre was opened in Cardiff in 2002. The aim of this paper is to report student perspectives and opinions on their experience at this unit over a 5-year period. METHODS: Final year dental students at Cardiff University were invited to report their comments on the St David's Primary Care Unit at various times during their placement there. Information was recorded for undergraduate students who commenced final year in 2003, 2004, 2005, 2006 and 2007 (n = 257). RESULTS: After 1 year, the most common favourable aspects reported by students included the availability of a suitably trained nurse for all procedures (n = 191), ready access to helpful/approachable teaching staff (n = 145), and closeness of learning experience to subsequent practice (n = 122). Many students commented on their growing confidence in their own abilities whilst in the unit. CONCLUSION: Overwhelmingly, students reported their enthusiasm for training in an outreach teaching unit, preferring it to traditional dental school environments. Inherent in the comments recorded for each student was a sense of growing confidence in their abilities and development of reflective practice. Further work is needed to identify the impact of this form of dental student training on subsequent practices in Vocational Training and independent clinical careers.

Evaluating undergraduate preclinical operative skill; use of a glance and grade marking system.

OBJECTIVES: The purpose of the study was to evaluate the intra- and inter-examiner variability of a panel of examiners using a 'glance and grade' marking system when assessing Class II preparations. METHODS: The examination panel consisted of five university staff with varying clinical and teaching experience. The panel assessed 75 disto-occlusal preparations suitable for restoration with dental amalgam prepared in extracted human premolar teeth. The majority of the preparations were cut by undergraduates in their preclinical year of study and the remainder by an experienced staff member. The panel were blind to the identity of each operator. RESULTS: The study revealed a high degree of both intra- and inter-examiner variability, with some preparations being given a pass on one occasion and a fail on another and vice-versa. In addition, some of the panel, perhaps assuming that the practical exercise had been prepared entirely by undergraduates, were reluctant to award good grades. CONCLUSIONS: The study has highlighted the need for better staff training and a more comprehensive system of assessing preclinical skills.

Personal computers in forensic psychiatry.

Because forensic psychiatry is a relatively small field, there are few computer applications designed particularly for it. Forensic psychiatrists use personal computer in many ways that are similar to other psychiatrists, but certain aspects of forensic practice, such as an emphasis on precise reports, regular interactions with attorneys, use of legal databases and materials, and travel, call for utilizing available programs in different ways. Since forensic psychiatry draws on the knowledge of psychiatry, law, and criminology, the World Wide Web has become a particularly useful resource for information. An array of applications and resources of particular interest to forensic psychiatrists are presented. Computer education, "telemedicine," and teleconferencing are still in their infancy in forensic psychiatry, but are likely to increase in use as these technologies mature.

Forensic child and adolescent psychiatry: a review of the past 10 years.

OBJECTIVE: To review important developments in child and adolescent forensic psychiatry from 1987 through 1996. METHOD: Major changes in the law and developments in research and practice were surveyed in the areas of the legal regulation of psychiatry, family law (divorce and child abuse), consultation to juvenile and criminal courts, civil litigation, and the development of the subspecialty. RESULTS: There has been a large increase in research based on quantifiable descriptive data of forensic populations, although studies using comparison or control groups remain relatively rare. While managed care has heavily influenced treatment practice, legal liability remains largely with the clinician. Issues regarding techniques of evaluation for sexual abuse have been scrutinized by the courts and by researchers. Legislative responses to rising rates of juvenile violence have been in the direction of treating violent adolescent offenders as criminally responsible adults. There has been a major move toward setting standards for forensic evaluations, training, and credentials. CONCLUSIONS: Child and adolescent forensic psychiatry remains an area encompassing diverse clinical issues. It remains unclear the extent to which it will develop into a formal subspecialty.

Gun acquisition and use by juvenile offenders.

OBJECTIVES: To learn how, when, where, and why juvenile offenders acquire guns. DESIGN: Following acquisition of informed consent, we conducted semistructured interviews between June and November 1995 with a convenience sample of 63 juvenile offenders aged 13 through 18 years, each of whom was incarcerated at a detention center in metropolitan Atlanta, Ga. SETTING: Five detention centers in metropolitan Atlanta. MAIN OUTCOME MEASURES: Frequency of handgun acquisition and use, age at and method of first handgun acquisition, feelings experienced when carrying guns, development of gun-carrying behavior, drug use, and gang membership. RESULTS: The mean age of respondents was 15.7 years. Forty-one male and 12 female respondents had owned a gun. Eighty-four percent of gun carriers acquired their first gun before the age of 15 years; more than half received their first gun passively, without any specific plan to do so. Adolescents who purposefully obtained their first handgun were more likely to become frequent or constant carriers. Forty percent felt safer and 40% said they felt more energized, excited, or powerful while carrying a gun. However, 34% reported increased anxiety about getting caught. Almost all stated that guns are readily available from a wide range of sources. CONCLUSION: Knowledge of the developmental patterns of gun carrying by delinquent adolescents could be useful in formulating effective strategies to reduce firearm violence.

Predictors of returning to work.

An investigation of predictors of returning to work in a sample of physically injured persons who are receiving workers' compensation benefits and vocational rehabilitation is presented. One hundred fourteen injured subjects (86 with back injury; 28, other injury) undergoing vocational rehabilitation and receiving workers' compensation benefits were assessed on demographic, emotional, cognitive, financial incentive, and miscellaneous variables. Predictors for returning to work were identified using stepwise logistic regression. Patients with moderate or severe depression, defined as a score greater than 16 on the Beck Depression Inventory (BDI), were significantly less likely to return to work following vocational rehabilitation efforts than patients with less severe depression (for back-injured patients, odds ratio (OR) = 31, 95% CI [8.8, 108]). BDI scores correctly classified 84 percent of the back-injury and 86% of the other-injury groups with respect to their return to work. The level of workers' compensation benefit was the only variable that added (marginally) to the predictive power of the BDI. In a physically injured population receiving workers' compensation benefits, who are judged to be not clearly permanently disabled, level of depressive symptoms is a strong predictor of returning to work. Caution is warranted in using the BDI as the sole determinant in a forensic situation for making a real-world prediction, as BDI responses are easy to fake. Treatment of concurrent depression is an important component of helping physically injured workers resume gainful employment.

Pharmacokinetics of antiviral polyoxometalates in rats.

Polyoxometalates are soluble mineral compounds formed principally of oxide anions and early transition metal cations. The polyoxometalates K12H2[P2W12O48].24H2O (JM 1591), K10[P2W18Zn4(H2O)2O68].20H2O (JM 1596), and [(CH3)3NH]8[Si2W18Nb6O77] (JM 2820) demonstrate potent antiviral activity against human immunodeficiency virus types 1 and 2, herpes simplex virus, and cytomegalovirus in vitro. The preclinical pharmacokinetics of these three compounds were characterized after single-dose intravenous administration of 50 mg/kg to rats. Plasma, urine, and feces were collected for 168 h, and polyoxometalate concentrations were determined by atomic emission. Serum protein binding was measured by equilibrium dialysis. All three compounds were highly bound to serum proteins in a concentration-dependent manner. Total and unbound concentrations of the three compounds in plasma declined in a triexponential manner with terminal half-lives of 246.0 +/- 127.0, 438.4 +/- 129.4, and 32.2 +/- 5.37 h (mean +/- standard deviation) for JM 1591, JM 1596, and JM 2820, respectively. Systemic clearances based on total concentrations in plasma were low, averaging 0.016 +/- 0.002, 0.015 +/- 0.002, and 0.018 +/- 0.003 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. The clearances of unbound compounds from plasma averaged 0.966 +/- 0.136, 0.050 +/- 0.005, and 0.901 +/- 0.165 liter/h/kg for JM 1591, JM 1596, and JM 2820, respectively. For JM 1596, the clearance of unbound compound from the kidneys was lower than the glomerular filtration rate (0.086 liter/h/kg), suggesting this polyoxometalate underwent renal tubular reabsorption. However, JM 1591 and JM 2820 appeared to undergo tubular secretion. The fraction of the dose recovered in urine was 11.5, 46.8, and 10.6% for JM 1591, JM 1596, and JM 2820, respectively. Approximately 5% of the dose of each polyoxometalate was recovered in feces. The steady-state volume of distribution based on total concentrations averaged 1.44 liters/kg for JM 1591, 2.39 liters/kg for JM 1596, and 0.59 liter/kg for JM 2820, indicating moderate to wide distribution throughout the body. All three compounds were detected in various tissues 1 week after single-dose administrations, with the highest levels found in the kidneys and liver. The results of this study indicate that the disposition of polyoxometalates is highly dependent on their molecular structure.

Secretion of adrenocorticotrophin (ACTH) and ACTH precursors in ovine anterior pituitary cells: actions of corticotrophin-releasing hormone, arginine vasopressin and glucocorticoids.

Although corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) have been extensively characterized as stimulators, and glucocorticoids as inhibitors of ACTH secretion, far less is known about the control of the secretion of ACTH precursors from the anterior pituitary or about the types of corticotrophs involved. The present study was designed to systematically evaluate the actions of stimulatory and inhibitory factors on the secretion of ACTH and ACTH precursors (pro-opiomelanocortin, M(r) 31,000; pro-ACTH, M(r) 22,000) from dissociated ovine anterior pituitary cells. The cells were stimulated for 3 h with CRH (10 nmol/l) and AVP (100 nmol/l), alone or in combination with the synthetic glucocorticoid dexamethasone. In designated wells, cells were treated with dexamethasone, (100 nmol/l), beginning 16-18 h before and continuing through the 3-h secretion experiments in the presence of CRH and AVP. Secretion of ACTH-like peptides from intact cultures was compared with that from cultures which had been pretreated with a cytotoxic CRH conjugate (cytotoxin) to eliminate CRH-target cells specifically. Immunoreactive (ir)-ACTH was measured by radioimmunoassay (RIA); ACTH(1-39) and ACTH precursors were specifically measured by two-site immunoradiometric assays that discriminate between the two. In intact populations of cells, dexamethasone had no effect on basal ACTH(1-39) secretion, but decreased the secretion of ACTH(1-39) in response to CRH or AVP. Pretreatment of cells in the same experiments with cytotoxin (for 18 h, beginning 3.5 days before secretion studies) also had no significant effect on basal ACTH(1-39) secretion, but eliminated the response to CRH and decreased the response to AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Biased reporting by parents undergoing child custody evaluations.

This study tested the hypothesis that a parent undergoing a child custody evaluation will bias his or her report of the children's symptoms in a direction that supports the parent's aim in the litigation. Parents in 196 court-ordered child custody evaluations rated their children using the Achenbach Child Behavior Checklist. Additional families undergoing evaluations of visitation disputes (N = 34) and custody/visitation disputes complicated by sexual abuse allegations (N = 15) were used as comparison groups to test alternative explanations of the findings. Results were strongly supportive of the hypothesis that parental bias was present and quantifiable.

Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells.

Monocyte-macrophage polypeptides (monokines) cause synovial cells to increase the levels of putative mediators of destruction and inflammation. This interaction may account for some of the properties of rheumatoid pannus. We report here that samples of purified human interleukin-1 beta (IL-1 beta) and recombinant IL-1 alpha stimulate both the plasminogen activator activity and prostaglandin E2 levels of human synovial fibroblast-like cells. The same holds true for purified pig IL-1 (catabolin) and recombinant murine IL-1. The elevation in plasminogen activator activity was inhibited by indomethacin, and this suggests that endogenous prostanoids are important in the IL-1-mediated stimulation of proteinase activity.

Interleukin-1 beta and interleukin-1 alpha stimulate the N-acetyl-beta-glucosaminidase activity of human synovial cells.

The properties of synovial cells are altered in vitro by monocyte-macrophage polypeptides (monokines), and these changes could explain some of the properties of the inflamed synovium in rheumatoid disease. Purified monokines have become available only recently for testing on the target synovial cells. We report here that purified human interleukin (IL)-1 beta and recombinant human IL-1 alpha stimulate the extracellular activity of the lysosomal hydrolase, N-acetyl-beta-glucosaminidase (NAG), of human synovial fibroblast-like cells. In contrast, another monokine, synovial activator, does not increase the NAG activity. Thus NAG is another cellular activity which can be modulated by interleukin-1.