Cause for concern: BDA v GDC.

In this Opinion article I will discuss the relationship between the BDA and the GDC, the nature of the BDA's and dentists' language when communicating with the GDC and when discussing the GDC in public forums, such as this journal. I also suggest ways this relationship can be improved for the benefit of dentists and the GDC.

A randomized clinical study to assess ingestion of dentifrice by children.

This study investigated whether there was a difference in amounts of dentifrice ingested by children based on age using pea-sized instructions. The study had a randomized, single-blinded, 3-period, crossover design modelled after Barnhart et al. (1974) with one regular-flavored and two specially-flavored dentifrices used ad libitum. Subjects were enrolled in three groups: 2-4, 5-7, and 8-12 years. They were instructed to brush at home as they would normally with each dentifrice for 3 weeks (9 weeks total). On weekly study-site visits, subjects brushed with the assigned dentifrice containing a lithium marker to measure the amount of dentifrice ingested and used. Averaging across dentifrices, amounts ingested were: 0.205 g (2-4 yr), 0.125 g (5-7 yr) and 0.135 g (8-12 yr), demonstrating 2-4 year-olds ingested significantly more than older children (p ≤ 0.002). Averaging across dentifrices, amounts used were: 0.524 g (2-4 yr), 0.741 g (5-7 yr) and 0.978 g (8-12 yr) suggesting an age-related effect (p < 0.01). Findings also showed that ingestion amount for specially-flavored dentifrices may increase relative to regular-flavored dentifrice for children 2-7 years-old. This research demonstrated that dentifrice ingestion amount decreased significantly with age while usage amount increased with age. Importantly, ingestion and usage levels in younger children reflect "pea-sized" direction and were numerically lower than historical levels reported prior to this direction.

The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis.

Predicting and understanding the mechanism of drug-induced toxicity is one of the primary goals of drug development. It has been hypothesized that inflammation may have a synergistic role in this process. Cell-based models provide an easily manipulated system to investigate this type of drug toxicity. Several groups have attempted to reproduce in vivo toxicity with combination treatment of pharmacological agents and inflammatory cytokines. Through this approach, synergistic cytotoxicity between the investigational agent pevonedistat (MLN4924) and TNF-α was identified. Pevonedistat is an inhibitor of the NEDD8-activating enzyme (NAE). Inhibition of NAE prevents activation of cullin-RING ligases, which are critical for proteasome-mediated protein degradation. TNF-α is a cytokine that is involved in inflammatory responses and cell death, among other biological functions. Treatment of cultured cells with the combination of pevonedistat and TNF-α, but not as single agents, resulted in rapid cell death. This cell death was determined to be mediated by caspase-8. Interestingly, the combination treatment of pevonedistat and TNF-α also caused an accumulation of the p10 protease subunit of caspase-8 that was not observed with cytotoxic doses of TNF-α. Under conditions where apoptosis was blocked, the mechanism of death switched to necroptosis. Trimerized MLKL was verified as a biomarker of necroptotic cell death. The synergistic toxicity of pevonedistat and elevated TNF-α was also demonstrated by in vivo rat studies. Only the combination treatment resulted in elevated serum markers of liver damage and single-cell hepatocyte necrosis. Taken together, the results of this work have characterized a novel synergistic toxicity driven by pevonedistat and TNF-α.

Effective half-life of caesium-137 in various environmental media at the Savannah river site.

During the operational history of the Savannah River Site (SRS), many different radionuclides have been released from site facilities into the SRS environment. However, only a relatively small number of pathways, most importantly (137)Cs in fish and deer, have contributed significantly to doses and risks to the public. The "effective" half-lives (Te) of (137)Cs (which include both physical decay and environmental dispersion) in Savannah River floodplain soil and vegetation and in fish and white-tailed deer from the SRS were estimated using long-term monitoring data. For 1974-2011, the Tes of (137)Cs in Savannah River floodplain soil and vegetation were 17.0 years (95% CI = 14.2-19.9) and 13.4 years (95% CI = 10.8-16.0), respectively. These Tes were greater than in a previous study that used data collected only through 2005 as a likely result of changes in the flood regime of the Savannah River. Field analyses of (137)Cs concentrations in deer collected during yearly controlled hunts at the SRS indicated an overall Te of 15.9 years (95% CI = 12.3-19.6) for 1965-2011; however, the Te for 1990-2011 was significantly shorter (11.8 years, 95% CI = 4.8-18.8) due to an increase in the rate of (137)Cs removal. The shortest Tes were for fish in SRS streams and the Savannah River (3.5-9.0 years), where dilution and dispersal resulted in rapid (137)Cs removal. Long-term data show that Tes are significantly shorter than the physical half-life of (137)Cs in the SRS environment but that they can change over time. Therefore, it is desirable have a long period of record for calculating Tes and risky to extrapolate Tes beyond this period unless the processes governing (137)Cs removal are clearly understood.

Hyperthermic perfusion during cardiopulmonary bypass and postoperative temperature are independent predictors of acute kidney injury following cardiac surgery.

Acute kidney injury (AKI) following cardiopulmonary bypass (CPB) is associated with increased mortality, requirement for dialysis, and longer intensive care unit (ICU) and hospital length of stay. Rewarming during CPB and poor oxygen delivery have been associated with AKI; however, the role of temperature management on AKI has not been clearly defined. This study aims to evaluate the role of hyperthermia during CPB and the temperature upon admission to the ICU on AKI following cardiac surgery, using the RIFLE (renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease) criteria. To determine whether CPB hyperthermia (measured as the cumulative time the arterial outlet temperature >37°C) and ICU admission temperature were independent risk factors for AKI, data from 1393 consecutive adult patients undergoing isolated on-pump coronary artery bypass graft (CABG), valve repair and/or replacement and valve/CABG procedures was analysed using a logistic multivariate model. After testing for interaction, we incorporated covariates having a p-value <0.1. AKI was defined according to the RIFLE criteria as an increase in serum creatinine >50% from baseline to peak value postoperatively. Overall, 12.3% of patients developed AKI with a 4.5-fold increase in in-hospital mortality. Variables found to be independent predictors of AKI included CPB hyperthermia (Odds ratio [OR] 1.03 per minute increase [95% confidence interval (CI) 1.01-1.05]; p = 0.01), ICU admission temperature ([OR] 1.44 per degree increase [(CI) 1.13-1.85]; p<0.001), minimum CPB haemoglobin ([OR] 0.83 per g/dL increase [(CI) 0.71-0.97]; p = 0.02), use of intra-aortic balloon pump ([OR] 2.69 [(CI) 1.24-5.82]; p = 0.01) and ICU readmission ([OR] 3.13 [(CI) 1.73-5.64]; p<0.001). Avoiding arterial outlet hyperthermia may help decrease AKI following cardiac surgery using CPB. Both intraoperative and postoperative temperature management strategies should be the focus of future randomised studies to determine optimal interventions.

Effect of aripiprazole versus haloperidol on PANSS Prosocial items in early-episode patients with schizophrenia.

BACKGROUND AND AIM: Improving social functioning is critically important in early-episode schizophrenia, if patients are to achieve functional recovery. This post-hoc, pooled analysis of two studies compared the effect of aripiprazole versus haloperidol on social functioning in early-episode schizophrenia. METHODS: Data were pooled from two 52 week, randomized (2:1), double-blind, multicenter studies involving 1294 patients with chronic schizophrenia who were in an acute psychotic episode and had a history of positive antipsychotic response during previous episodes. The early-episode group was defined as patients who are

Continous quality improvement of perfusion practice: the role of electronic data collection and statistical control charts.

In-hospital data collection may be used to improve the selection, operative techniques, and process of care for cardiac surgical patients. The aim of this report is to demonstrate the influence of the automated generation of quality indicators (QI) for cardiopulmonary bypass (CPB) and the implementation of a continuous quality improvement (CQI) programme on the CPB process of care. Adult patients undergoing CPB were divided into three consecutive groups: Group 1 (n = 363); no QI data feedback, Group 2 (n = 253); automated QI data feedback alone, and Group 3 (n = 363) data feedback and implementation of CQI. There were no significant differences in demographic, procedural or clinical outcomes for each group. Significant improvement, as determined by adherence to practice protocols and reduction in practice variation, was observed for cardiac index < 1.6 L/min/m2 (min), mean arterial pressure < 40 mmHg (min), venous saturation < 60% (min), arterial blood temperature of > 37.5 degrees C (min), minimum pCO2 (mmHg), maximum pCO2 (mmHg), and minimum pO2 (mmHg). There was no change in the minimum haemoglobin (g/dl) on bypass. Automated generation of QI resulted in improved adherence to process of care guidelines, highlighting the potential of electronic data collection. This technique is optimised in a CQI programme, utilising statistical control charts for data interpretation.

To screen, or not to screen,--that is the question.

Recent studies of school dental screening and general dental practice in the North West of England may have provided an evidence base for the review of dental school screening and its improvement by increasing: the relevance of referral criteria, the rate of attendance resulting from screening, and treatment rates following referral--rather than for abandoning the process altogether.

Electronic data processing: the pathway to automated quality control of cardiopulmonary bypass.

Electronic data collection during cardiac surgery creates an enormous data source that has many potential applications. After the introduction of the Stockert Data Management System (DMS; Munich, Germany) to our perfusion practice, we recognized that the data could be used for the purpose of quality control (QC). Our aim was to create an automated technique of data analysis and feedback for cardiopulmonary bypass (CPB) procedures. Using visual basic programming, we created a process by which data from the DMS is analyzed and processed in a Microsoft Access database after a CPB procedure. The processing is designed to transfer the collected data to a research database and create a number of CPB quality indicator (QI) parameters, such as mean arterial pressure being less than 40 mmHg for more than 5 minutes or a venous saturation of less than 60% for more than 5 minutes. In the event of QI parameter detection, a QC report is generated and e-mailed to the senior perfusionist and the perfusionist performing the procedure. The introduction of electronic data collection and subsequent development of electronic data processing techniques has enabled us to transfer the data into a readily accessible database and create a data set of perfusion variables and quality indicators for CPB procedures. This data set may be used for immediate automated QC feedback after CPB procedures and direction of performance improvement initiatives through retrospective or prospective data analysis as part of a continuous quality improvement process.

A syndromal analysis of neuropsychological outcome following coronary artery bypass graft surgery.

BACKGROUND: Studies of neuropsychological outcome following coronary artery bypass graft surgery (CABG) have traditionally dichotomised patients as "impaired" or "unimpaired". This conceals the potential heterogeneity of deficits due to different mechanisms and sites of brain injury. OBJECTIVES: To explore neuropsychological outcome following CABG and determine to what extent it conforms to prototypic cortical and/or subcortical neurobehavioral syndromes and whether different intraoperative physiologic measures are associated with different subtypes of neuropsychological outcome. METHODS: Neuropsychological tests were administered to 85 patients before and after elective CABG and to 50 matched normal control subjects. Pre- to postoperative change scores were computed using standardised regression based norms. Change scores on selected memory measures were subjected to cluster analysis to identify qualitatively distinct subtypes of memory outcome. Emergent clusters were compared on non-memory measures, intraoperative physiologic measures, and demographic variables. RESULTS: Three subtypes of memory outcome were identified: memory spared (48% of patients), retrieval deficit (35%), and encoding/storage deficit (17%). Contrary to expectation, the subgroups were indistinguishable on measures of confrontation naming and manual dexterity and on intraoperative cardiac surgical physiologic measures and demographic variables. The encoding/storage deficit subgroup exhibited executive dysfunction. CONCLUSIONS: Heterogeneous profiles of neuropsychological dysfunction were found following CABG although they did not tightly conform to prototypic cortical and subcortical neurobehavioral syndromes. This challenges the value and appropriateness of the common practice of collapsing individual test scores to arrive at a single figure to define "impairment". Whether different subtypes of neuropsychological outcome are caused by different pathophysiologic mechanisms remains unknown.

The dental role in smoking cessation advice for patients with mental and behavioural disorders--time for improvement?

The past few years have seen an increasing emphasis upon the role of the dental team in smoking cessation. The recent advances in knowledge of the level and role of tobacco use in patients with mental and behavioural disorders, the biological factors involved and the influences of tobacco on psychiatric medication metabolism and side effects has not been reflected in dental postgraduate education. Perhaps it is time for an evidence based improvement in care standards by referring these patients for specialist cessation advice?

Removal of glucose from the cardiopulmonary bypass prime: a prospective clinical audit.

To quantify our decision for the removal of glucose and the use of mannitol as a substitute osmotic agent in the cardiopulmonary bypass prime, we conducted a prospective clinical audit to evaluate the effects of this change on patient outcomes. Data were prospectively collected for 172 consecutive routine cardiac surgery patients. The first 85 patients (Surgeon A, 42 patients [Group 1], Surgeon B, 43 patients [Group 2]) received 1000 mL Plasmalyte 148 + 5% glucose as per institutional protocol. The remaining priming volume for each group consisted of 500 mL hemaccel or 4% albumin, 50 mL 8.4% sodium bicarbonate, 100 mL Hartmann's solution. The change to a glucose-free prime was then initiated, substituting Plasmalyte 148 (without 5% glucose) for the Plasmalyte 148 + 5% glucose, in addition 12.5 g mannitol was administered following delivery of cardioplegia to the patients operated on by Surgeon B. Surgeon A would not include mannitol at this time. Forty-one patients operated by Surgeon A (Group 3) subsequently received Plasmalyte 148, and 46 patients operated on by Surgeon B (Group 4) received Plasmalyte 148 plus mannitol. Analysis was performed stratified by surgeon to quantify the effects of removing glucose from the prime. Comparisons were made between groups 1 and 3, and 2 and 4. Net fluid changes were recorded from pre-CPB, up to 24-h postoperatively. Intraoperative data collection included serum glucose, hematocrit, osmolality, return to rhythm, arrhythmias, and blood transfusions. Post-operative variables, including cardiac enzymes, arrhythmias, intubation time, length of stay, and mortality were also collected. Removal of glucose from the CPB prime resulted in a lower serum glucose concentration (mmol/L) during CPB (Gp 1 [13.6] vs. Gp 3 [5.4]; Gp 2 [14.7] vs. Gp 4 [5.4], p < .05). The addition of 12.5 g of mannitol to the CPB prime resulted in a significantly lower net fluid gain (mL) 24 h postoperatively (Gp 2[2792] vs. Gp 4 [1970], p < .05) and greater CPB hematocrit (%) (Gp 2 [24.3] vs. Gp 4 [26], p < .05). No other results were found to be significant (except CPB plasma osmolality (Groups 2 and 4) and sodium concentration [Groups 1 and 3]). The results of our audit provide an evidence base to support our change in practice to utilize nonglucose primes.

Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults.

BACKGROUND: Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants. METHODS: Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment) or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA), plasma glutathione peroxidase (GPX) and ferric reducing ability of plasma (FRAP). Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis. RESULTS: Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration. CONCLUSIONS: The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.

Coronary artery baroreceptor-mediated changes in arterial pressure: a pilot study in conscious and anaesthetized sheep.

1. Evidence suggesting the presence of coronary artery baroreceptors on coronary arteries has existed for over 30 years. 2. Evidence that activation of ventricular mechanoreceptors can elicit cardiovascular changes has been challenged, with those changes now thought to be due to coronary artery mechanoreceptors. 3. Studies have suggested that coronary artery mechanoreceptors act as coronary baroreceptors with a role in cardiovascular regulation. However, all evidence to date has been obtained in anaesthetized animal models in physiologically compromised intra-operative states. 4. The purpose of the present study was to design an ovine model that would allow the discrete stretch of coronary arteries without causing ischaemia or changing flow or intra-arterial pressure and that would confirm results seen in previous studies. In addition, the possibility that the technique could be used for studies of coronary artery baroreflexes in conscious sheep was investigated. 5. Controlled stretch of the proximal left anterior descending coronary artery elicited decreases in arterial pressure without changes in heart rate or electrocardiographic activity in halothane-anaesthetized sheep. Similar results were demonstrated in conscious sheep after surgical recovery of up to 2 weeks. 6. The present study supports the possibility that coronary artery baroreceptors exist and likely have a role in cardiovascular regulation. The results of the present study in anaesthetized sheep are in agreement with previous results in anaesthetized animals, but also provide the first demonstration of coronary baroreceptor activity in a conscious animal model, underscoring the potential use of the model in the study of coronary artery baroreceptors in the intact animal.

Purification and characterization of a beta-glucosidase from Citrus sinensis var. Valencia fruit tissue.

A preliminary survey demonstrated activity for alpha-D-glucosidase, alpha-D-mannosidase, alpha-L-arabinosidase, beta-D-glucosidase, beta-D-xylosidase, and beta-D-galactosidase in orange fruit flavedo and albedo tissue. alpha-L-Rhamnosidase was not detected. Subsequently, a beta-glucosidase was purified from mature fruit rag tissue (composed of intersegmental septa, squeezed juice sacs, and fruit core tissue) of Citrus sinensis var. Valencia. The beta-glucosidase exhibited low levels of activity against p-nitrophenyl-beta-D-fucopyranoside (13.5%) and p-nitrophenyl-alpha-D-glucopyranoside (7.0%), compared to its activity against p-nitrophenyl-beta-D-glucopyranoside (pNPG, 100%). The enzyme was purified by a combination of ion exchange (anion and cation) and gel filtration (Superdex and Toyopearl HW-55S) chromatography. It has an apparent molecular mass of 64 kDa by denaturing electrophoresis or 55 kDa by gel filtration chromatography (BioGel P-100). Hydrolysis of pNPG demonstrated a pH optimum between 4.5 and 5.5. At pH 5.0 the temperature optimum was 40 degrees C. At pH 5.0 and 40 degrees C the K(m) for pNPG was 0.1146 mM and it had a V(max) of 5.2792 nkatal x mg(-1) protein (katal = 0.06 International Units = the amount of enzyme that produces, under standard conditions, one micromol of product per min). Of the substrates tested, the enzyme was most active against the disaccharide cellobiose (1-->4), but was not active against p-nitrophenyl-beta-D-cellobioside. High levels of activity also were observed with the disaccharides laminaribiose (1-->3), gentiobiose (1-->6), and sophorose (1-->2). Activity greater than that observed with pNPG was obtained with the flavonoids hesperetin-7-glucoside and prunin (naringenin-7-glucoside), salicin, mandelonitrile-beta-D-glucoside (a cyanogenic substrate), and sinigrin (a glucosinolate). The enzyme was not active against amygdalin, coniferin, or limonin glucoside.