Effect of high-speed sintering on the properties of a zirconia material.

Digital dentistry has led to the success of same-day, single-crown delivery. Unlike traditional convection furnaces for fabrication of zirconia materials, which typically require several hours to complete sintering, a dedicated high-speed sintering furnace that reportedly sinters zirconia in minutes is now available. Sintering times may increase or decrease based on the size of the restoration due to a novel interface between the chairside acquisition unit, milling unit, and furnace. The purpose of this study was to compare the flexural properties (strength and modulus), optical parameters (translucency and opalescence), and grain size of a full-contour tetragonal zirconia material after sintering in either a novel high-speed furnace or a conventional zirconia furnace. Rectangular zirconia beams were milled and sintered using the high-speed induction furnace for 26.2 minutes or a conventional convection furnace for 4.3 hours. Flexural strength and modulus were determined by subjecting the beams to a 3-point bending test in a materials testing machine. Translucency and opalescence were calculated using a spectrophotometer, and grain size was determined by using an atomic force microscope. The dedicated high-speed induction furnace sintered the tetragonal zirconia specimens in substantially less time than the conventional convection furnace, with a statistically significant decrease in grain size and no significant difference in strength or optical properties.

Career intentions of medical students trained in six sub-Saharan African countries.

INTRODUCTION: Sub-Saharan Africa(SSA) is the world region worst affected by physician migration. Identifying reasons why medical students wish to stay or leave Africa could assist in developing strategies which favour retention of these graduates. This study investigated the career intentions of graduating students attending medical schools in SSA to identify interventions which may improve retention of African physicians in their country of training or origin. METHODS: Final year medical students attending nine medical schools in SSA were surveyed--students from four schools in South Africa and one school each in the Democratic Republic of Congo, Kenya, Nigeria, Tanzania and Uganda. The response rate was 78.5% (990 of 1260 students); data from the 984 students who indicated they were remaining in medicine were entered into a database, and descriptive statistics were obtained. RESULTS: Most (97.4%) of the 984 responding students were African by birth. The majority (91.2%) intended to undertake postgraduate training; the top three specialty choices were surgery (20%), internal medicine (16.7%), and paediatrics (9%). Few were interested in family medicine (4.5%) or public health (2.6%) or intended to practice in rural areas (4.8%). Many students (40%) planned to train abroad. About one fifth (21%) intended to relocate outside sub-Saharan Africa. These were about equally divided between South Africans (48%) and those from the other five countries (52%). The top perceived career-related factors favouring retention in Africa were career options and quality and availability of training opportunities. Several factors were reported significantly more by South African than the other students. The top personal factors for staying in Africa were a desire to improve medicine in Africa, personal safety, social conditions and family issues. The top career-related factors favouring relocation outside Africa were remuneration, access to equipment and advanced technology, career and training opportunities, regulated work environment and politics of health care in Africa. Several of these were reported significantly more by students from the other countries as compared with South Africans. The top personal factors favouring relocation outside Africa were personal safety, opportunity for experience in a different environment, social conditions and greater personal freedom. DISCUSSION: The career intentions of African medical students are not aligned with the continent's health workforce needs. A number of interventions that warrant further attention were identified in this study.

Intrathecal morphine provides effective and safe analgesia in children after cardiac surgery.

BACKGROUND: The purpose of this prospective, randomized, blinded to observer study was to assess the analgesic effect and safety of intrathecal morphine (ITM) in post-operative pain control in children after heart surgery with a sternotomy incision. METHODS: Eighty children, 3-55 kg in body weight, undergoing elective cardiac surgery with opioid-based anaesthesia were randomly divided into two treatment groups to receive either 20 micrograms/kg ITM at induction of anaesthesia or control. To standardize the protocol for administration of post-operative rescue intravenous morphine boluses and infusion (20-60 micrograms/kg/h), the Cardiac Analgesic Assessment Scale (CAAS) was used. RESULTS: Nine patients were excluded from the study after randomization. Thirty-five patients were enrolled to the ITM group and 36 to the control group. The groups were similar for demographics and intra-operative clinical characteristics. The mean time for the first intravenous morphine dose from ITM administration or equivalent time zero in the control group was significantly longer (P = 0.003) in the ITM group compared with the control group (12.3 vs. 8.7 h). Time from Paediatric Intensive Care Unit (PICU) admission to the start of intravenous morphine was also significantly longer (P = 0.01) in the ITM group (6.0 vs. 3.4 h). The total intravenous morphine consumption over the mean 19 post-operative hours was significantly lower (P = 0.03) in the ITM group. However, the use of ITM did not result in earlier extubation or earlier discharge from the PICU. Of the 35 patients who received ITM at induction of anesthesia, 20% (n = 7) did not require any additional morphine in the PICU compared with three out of 36 control group patients. This did not reach statistical significance. The incidence of adverse events was low in both groups. CONCLUSIONS: An ITM dose of 20 micrograms/kg had a significant (P = 0.03) intravenous morphine-sparing effect after cardiac surgery. Effective analgesia was observed for 12 h after administration of intrathecal morphine.

Human apolipoprotein E4 accelerates beta-amyloid deposition in APPsw transgenic mouse brain.

The human apolipoprotein E4 (ApoE4) isoform is associated with genetic risk for Alzheimer's disease. To assess the effects of different ApoE isoforms on amyloid plaque formation, human ApoE3 and ApoE4 were expressed in the brains of transgenic mice under the control of the human transferrin promoter. Mice were crossed with transgenic mice expressing human amyloid precursor protein containing the Swedish mutation (APPsw), which facilitates amyloid beta peptide (A beta) production. The following progeny were selected for characterization: APPsw+/- x ApoE3+/- and APPsw+/-, APPsw+/- x ApoE4+/- and APPsw+/- littermates. All mice analyzed were wild type for the endogenous mouse APP and ApoE genes. Mice expressing ApoE4 in combination with APPsw have accelerated A beta deposition in the brain as assessed by enzyme immunoassay for A beta40 and A beta42 extractable in 70% formic acid, by assessment of amyloid plaque formation using thioflavin-S staining, and by immunohistochemical staining with antibodies specific for A beta40 or A beta42 and the 4G8 monoclonal or 162 polyclonal antibody. No difference in the rate of A beta deposition in the brain was seen in mice expressing ApoE3 in combination with APPsw. Thus, our data are consistent with the observation in Alzheimer's disease that ApoE4 is associated with increased accumulation of A beta in the brain relative to ApoE3.

Validation of the doctor-patient communication component of the Educational Commission for Foreign Medical Graduates Clinical Skills Assessment.

BACKGROUND: The pivotal role of doctor-patient communication in effective health care delivery led the Educational Commission for Foreign Medical Graduates (ECFMG) to incorporate the assessment of interpersonal skills and spoken English proficiency into its Clinical Skills Assessment (CSA). Furthermore, it was decided that to pass the CSA, a candidate would need to meet or surpass defined performance standards for doctor-patient communication as a discrete component. This requirement, among others, is designed to ensure the readiness of graduates of foreign medical schools (FMGs) to enter postgraduate medical education programmes in the United States. OBJECTIVE: The primary focus of this study was to determine the extent to which performance in a simulated testing environment is related to performance in the clinical setting. METHOD: Nurses were trained to rate the communication skills of residents from the patient's perspective. A total of 43 first-year residents were evaluated. The survey ratings (n=225) were compared with the residents' CSA communication scores. RESULTS: Corrected correlations between CSA ratings and those obtained from nurses ranged from 0.61 to 0.73. CONCLUSION: This study provides evidence for the validity of the communication ratings provided by standardized patients. The reasonably strong associations between ratings obtained during testing and those obtained through observation of 'real' patient interactions suggest that external observers can provide accurate evaluations of doctor-patient communication.

Evaluating the spoken English proficiency of graduates of foreign medical schools.

PURPOSE: The purpose of this study was to gather additional evidence for the validity and reliability of spoken English proficiency ratings provided by trained standardized patients (SPs) in high-stakes clinical skills examination. METHOD: Over 2500 candidates who took the Educational Commission for Foreign Medical Graduates' (ECFMG) Clinical Skills Assessment (CSA) were studied. The CSA consists of 10 or 11 timed clinical encounters. Standardized patients evaluate spoken English proficiency and interpersonal skills in every encounter. Generalizability theory was used to estimate the consistency of spoken English ratings. Validity coefficients were calculated by correlating summary English ratings with CSA scores and other external criterion measures. Mean spoken English ratings were also compared by various candidate background variables. RESULTS: The reliability of the spoken English ratings, based on 10 independent evaluations, was high. The magnitudes of the associated variance components indicated that the evaluation of a candidate's spoken English proficiency is unlikely to be affected by the choice of cases or SPs used in a given assessment. Proficiency in spoken English was related to native language (English versus other) and scores from the Test of English as a Foreign Language (TOEFL). DISCUSSION: The pattern of the relationships, both within assessment components and with external criterion measures, suggests that valid measures of spoken English proficiency are obtained. This result, combined with the high reproducibility of the ratings over encounters and SPs, supports the use of trained SPs to measure spoken English skills in a simulated medical environment.

Effect of training location on students' clinical skills.

The clinical skills of second-year medical students trained in a hospital-based setting were compared with those of students trained in a community setting using an objective structured clinical exam. No statistically significant difference was found.

Evidence based practice: are critical care nurses ready for it?

In the emergence of the evidence based practice movement, critical care nurses have struggled to identify scientific evidence on which to base their clinical practice. While the lack of critical care nursing research is a major concern, other important issues have significantly stalled the implementation of evidence even when it is available. A descriptive study of 274 critical care nurses was undertaken to examine nursing research activity in Victorian critical care units. The study aimed to identify critical care nurses' research skills, the barriers encountered in participation and implementation and the current availability of resources. Results revealed that 42 per cent of the nurses who participated in the study believed that they were not prepared adequately to evaluate research, and less than a third believed they were sufficiently skilled to conduct valid scientific studies. An association was found between nurses' ability to confidently perform research activities and higher academic qualifications. The study found that there is a lack of organisational support and management commitment for the development of evidence based nursing. In order to facilitate the implementation of evidence based practice, clinicians must be made aware of the available resources, be educated and mentored when carrying out and using clinical research, and be supported in professional initiatives that promote evidence based practice. It is argued that this will have positive implications for patient outcomes in the critical care environment.

Nurses' experiences of caring for culturally and linguistically diverse families when their child dies.

Nurses experience the care of a dying child and their family as a challenging but distressing event. In a paediatric intensive care unit (PICU), Melbourne, Australia, nurses expressed a concern that they may not be providing the most appropriate care when a cultural disparity exists between nurses and families experiencing the death of their child. A critically informed study was undertaken with six PICU nurses to explore their experiences of caring for a culturally and linguistically diverse family whose child had died. Three consecutive focus group interviews were conducted with the nurses to identify issues in this area of their nursing practice and to contemplate how their practice might be changed. The focus of this paper is on one particular finding of the study about the nurses' use of controlling practices to ensure families conformed to the established routines and values of the PICU staff.

Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer's disease.

Beta-amyloid (Abeta) plaques have been shown to induce inflammatory changes in Alzheimer's disease brains. Cortical, but not cerebellar tissue from 16-month-old Tg2576 (Tg+) mice showed significant increases in interleukin (IL)-1alpha (2.2-fold), IL-1beta (3.4-fold), tumor necrosis factor-alpha (3.9-fold), and monocyte chemoattractant protein-1 (2.5-fold) mRNA levels compared to controls (Tg-). These changes were not apparent in 6-month-old Tg+ mice except for TNF-alpha. mRNA levels of glial fibrillary acidic protein and complement components, C1qA and C3 were also elevated in aged mice. Lipopolysaccharide (LPS) (25 microg/mouse, i.v.) induced a significantly greater production of IL-1beta protein in the cortices and hippocampi of Tg+ vs. Tg- mice at 1, 2, 4, and 6 h. Experiments in 6-month-old mice showed that not only was there less cytokine produced compared to 16-month-old mice, but the exacerbated cytokine response to LPS in Tg+ mice was not apparent. Higher levels of Abeta1-40 were measured in the cortices of 6- and 16-month-old Tg+ mice at 4-6 h after LPS, which returned to baseline after 18 h. We demonstrate that Abeta plaques elicit inflammatory responses in Tg2576 mice that are further exacerbated when challenged by an exogenous inflammatory insult, which may serve to amplify degenerative processes.

Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord.

Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis.

Cardiac tamponade after removal of atrial intracardiac monitoring catheters in a pediatric patient: case report.

The incidence of cardiac tamponade after cardiac surgery is reported as ranging from 0.04% to 7%. Although a relatively infrequent complication, tamponade is associated with significant morbidity and mortality. Reports of tamponade after pediatric cardiac surgery are few and generally associated with postcardiotomy syndrome or, less commonly, removal of left atrial or pulmonary artery catheters after surgery. A case is presented of cardiac tamponade in a pediatric patient resulting from removal of a direct atrial and a pulmonary artery catheter after cardiac surgery. The pathophysiology of cardiac tamponade is reviewed and the increased risk for pediatric patients is outlined. The case review is conducted in the context of existing policies in the reporting institution and recommendations for practice are discussed.

Cost effectiveness evaluation of ADCON-L adhesion control gel in lumbar surgery.

Patients, physicians and third-party payers are becoming increasingly concerned with the economic burden resulting from advances in health care. Many economic health studies have focused on patients with sciatica and low back pain. An Economic Survey was conducted on lumbar discectomy patients who had been enrolled at least 12 months prior in a prospective randomized controlled clinical study of the adhesion control device ADCON-L. The survey measured patient satisfaction, return to work, additional medical treatment and medications after surgery. In addition, the duration of any re-operations from patients in the clinical study was analyzed. The results of the Economic Survey and re-operation time analysis show significant advantages for lumbar discectomy patients who received ADCON-L compared to control patients who did not. Patients who received ADCON-L not only had less scarring and less back pain than control patients but also were more satisfied with their surgeries and were able to return to work more often, as originally planned (p = 0.02). In addition, ADCON-L patients returned to their original jobs an average of 3.6 days sooner, changed jobs 50% less often, did not seek additional medical treatment as often, and took 20% less pain medication than did control patients (p = 0.01). In addition, patients receiving ADCON-L who required subsequent re-operation at the same lumbar space (e.g., reherniation) had a significantly shorter duration of secondary surgery (56.6 min vs. 130 min, p = 0.001) compared to patients who did not receive ADCON-L at the first surgery. Overall, ADCON-L patients demonstrated significant clinical and economic advantages over control patients. If all lumbar surgical patients in the US were to receive ADCON-L, annual savings to the health care system would exceed one half billion dollars.

Microbial Contamination in Spodoptera littoralis Nuclear Polyhedrosis Virus Produced in Insects in Egypt

Spodoptera littoralis nuclear polyhedrosis virus produced in Egypt, for use in field trials for the control of S. littoralis on cotton, was subject to microbiological examination to quantify microbial contamination. Bacteria were found to be present at 10(6)-10(9) colony-forming units/ml in virus suspensions containing 2.1 x 10(9) polyhedral inclusion bodies/ml. Batches were found to contain between 2 and 11 different species of contaminant microbes. No primary human pathogens of medical importance were found. The dominant species were fecal Streptococci and two Bacillus species, B. cereus and B. sphaericus. The Streptococci were derived from the normal gut flora found in healthy insects; the Bacillus species were common opportunistic saprophytes which gained access to the product by colonizing dead larvae and diet waste. Purification methods based on centrifugation were found to be ineffective in removing bacteria and improved methods of hygiene and harvesting appeared to be of more value in reducing contamination.

Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.

Recent transcription mapping efforts within chromosome 17q21 have led to the identification of a human homolog of the Drosophila gene Enhancer of zeste, E(z). A member of the Polycomb group (Pc-G) of proteins, Drosophila E(z) acts as a negative regulator of the segment identity genes of the Antennapedia and Bithorax complexes. Here we report the full-length protein coding sequence of human EZH1 (Enhancer of zeste homolog 1) and compare the respective protein sequences in both species. EZH1 encodes a protein of 747 amino acids that displays 55% amino acid identity overall (70% similarity) with Drosophila E(z). The strongest homology was noted (79% identity, 89% similarity) within the carboxy-terminal 245 amino acids, including the SET domain, a region of E(z) also conserved in other Drosophila proteins with roles in development and/or chromatin structure. A large Cysrich region with a novel spatial pattern of cysteine residues was also conserved in both EZH1 and E(z). The strong sequence conservation suggest potential roles for EZH1 in human development as a transcriptional regulator and as a component of protein complexes that stably maintain heterochromatin. EZH1 is expressed as two major transcripts in all adult and fetal human tissues surveyed; comparison of cloned cDNAs suggests that alternative splicing may account for at least part of the transcript size difference. Analysis of one cDNA revealed an unusual splicing event involving EZH1 and a tandemly linked gene GPR2 and suggests a potential mechanism for modifying the EZH1 protein in the conserved C-terminal domain. The sequence and isolated cDNAs will provide useful reagents for determining the function of EZH1 and the importance of the evolutionarily conserved domains.

Enhancement by GABA of the association rate of picrotoxin and tert-butylbicyclophosphorothionate to the rat cloned alpha 1 beta 2 gamma 2 GABAA receptor subtype.

1. We examined how gamma-aminobutyric acid (GABA) influences interaction of picrotoxin and tert-butylbicyclophosphorothionate (TBPS) with recombinant rat alpha 1 beta 2 gamma 2 GABAA receptors stably expressed in human embryonic kidney cells (HEK293), as monitored with changes in Cl- currents measured by the whole-cell patch clamp technique. 2. During application of GABA (5 microM) for 15 s, picrotoxin and TBPS dose-dependently accelerated the decay of inward GABA-induced currents (a holding potential of -60 mV under a symmetrical Cl- gradient). The drugs, upon preincubation with the receptors, also reduced the initial current amplitude in a preincubation time and concentration-dependent manner. This indicates their interaction with both GABA-bound and resting receptors. 3. The half maximal inhibitory concentration for picrotoxin and TBPS at the beginning of a 15 s GABA (5 microM) pulse was several times greater than that obtained at the end of the pulse. GABA thus appears to enhance picrotoxin and TBPS potency, but only at concentrations leading to occupancy of both high and low affinity GABA sites, i.e., 5 microM. Preincubation of the receptors with the drugs in the presence of GABA at 200 nM, which leads to occupancy of only high affinity GABA sites in the alpha 1 beta 2 gamma 2 subtype, produced no appreciable change in potency of picrotoxin or TBPS. This indicates that they preferentially interact with multiliganded, but not monoliganded receptors, unlike U-93631, a novel ligand to the picrotoxin site, which has higher affinity to both mono- and multiliganded receptors than resting receptors. 4. The time-dependent decay and preincubation time-dependent reduction of initial amplitude of GABA-induced Cl- currents followed monoexponential time courses, and time constants thus obtained displayed a linear relationship with drug concentration. Analysis of the data using a kinetic model with a single drug site showed that GABA (5 microM) enhanced the association rate for picrotoxin and TBPS nearly 100 fold, but their dissociation rate only 10 fold. The dissociation rate obtained from current recovery from picrotoxin or TBPS block yielded nearly identical values to the above analysis.5. We conclude that picrotoxin and TBPS interact with both resting and GABA-bound receptors, but their affinity for the latter is about 10 times greater than that for the former, largely due to a markedly increased association rate to the multiliganded receptors (but not monoliganded ones). This and our earlier study with U-93631 improves our understanding of functional coupling between GABA and picrotoxin sites, which appears to be useful in characterizing the mode of interaction for various picrotoxin site ligands.

Interaction of beta-carboline inverse agonists for the benzodiazepine site with another site on GABAA receptors.

1. We examined the effects of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), a beta-carboline inverse agonist for the benzodiazepine site, on gamma-aminobutyric acid (GABA)-induced Cl-currents in several cloned rat GABAA receptor subtypes expressed in human embryonic kidney cells. The Cl- currents were measured in the whole cell configuration of patch clamp techniques. 2. DMCM at low concentrations (< 0.5 microM) occupying only the benzodiazepine site decreased GABA-induced Cl currents in the alpha 1 beta 2 gamma 2 and alpha 3 beta 2 gamma 2 subtypes as expected from an inverse agonist, but produced no change in the alpha 6 beta 2 gamma 2 subtype (perhaps a neutral antagonist). The drug at higher concentrations (> 0.5 microM) enhanced Cl- currents in all the subtypes with a half maximal concentration of 6 to 20 microM, depending on the alpha isoform. In the alpha 1 beta 2 subtype, which is without the benzodiazepine site, DMCM monophasically increased Cl- currents with a half maximal concentration of 1.9 microM. 3. Ro 15-1788 (a classical benzodiazepine antagonist) had no effect on Cl- current enhancement by DMCM and, in fact, increased the current level through blocking current inhibition by DMCM via the benzodiazepine site. Also, Cl- current enhancement by pentobarbitone or by 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one was additive to that by DMCM at saturating doses. It appears that the agonist site for DMCM is distinct from those for benzodiazepines, barbiturates and neurosteroids. 4. Among beta-carboline analogues, methyl-beta-carboline-3-carboxylate and propyl-beta-carboline-3-carboxylate markedly enhanced GABA-induced Cl currents in the alpha 1 beta 2 gamma 2 subtype, while N-methyl-beta-carboline-3-carboxamide and 1-methyl-7-methoxy-3,4-dihydro-beta-carboline did not. It appears that the 3-carboxyl ester moiety is necessary for beta-carbolines to interact with a novel site on GABAA receptors as agonists.

Cloning, sequence analysis and expression of two forms of mRNA coding for the human beta 2 subunit of the GABAA receptor.

Two forms of cDNA coding for the human GABAA beta 2 subunit have been cloned and sequenced. The two sequences differ by a 114 base pair insertion. The insert contains a phosphorylation consensus sequence for calmodulin-dependent protein kinase II. Quantitative PCR studies show that h beta 2L cDNA represents 10-15% of total h beta 2 cDNA in the 10 brain substructures tested. Analysis of human genomic southern blots suggests that the two forms might arise by differential splicing.