Do traditional sealants have a place in the new, super-magnified world?
The original concept of dental sealants is truly intoxicating... that an entry-level auxiliary could prevent occlusal caries by painting over the grooves of the teeth, thereby freeing up the doctor for more difficult tasks... all with a tidy profit. The realities of high-level magnification and research are sobering the "sealant euphoria." Today, we now understand that prevention of occlusal caries is significantly more complex and technically challenging than originally thought. Changing the process from a lower-skill, auxiliary-driven procedure to a high-skill, microscope-centered procedure will require a shift in scheduling and value systems. Earlier in the article I mentioned my nephew with the catastrophic sealant failures. Today he drives 4 hours to the airport and then flies another 2 hours so that he can receive a microscope-centered level of care (and pays in full). Microscope-enhanced dentistry is much more than simply making tiny little holes in teeth. It is a commitment to dentistry where vision is uncompromised, and today that level can best be attained with an operating microscope.


Studies on acute myelomonocytic leukemia in LBF1 rats.
Granulocytic leukemia was induced in Long-Evans (LE) rats by using the Huggins and Sugiyama method. After serial passage the cells became transformed. The newly transformed cells could be transplanted to LBF1 hybrid rats and observed more readily. A quantity of 10(8) cells/100 g body weight was injected intravenously and after 2-3 weeks myelomonocytic leukemia developed. By examining the bone marrow, spleen and lymph nodes, cytochemical tests verified this transformation. Transplanting 10(2)-10(4) cells under the renal capsule, a quickly growing solid tumor was observed, which caused metastasis to the parathymical lymph nodes and peritoneum. The investigation of oncogene expression for the myc and ras families revealed the presence of myc p62 and ras p21 oncoproteins in the tumor cells by using monoclonal antibodies in immunohistochemical tests. LBF1 rats proved to be good models in obtaining solid tumor growth and myelomonocytic leukemias, equivalent to human M4-M5 type leukemia.


Ligand affinity for amino-terminal and juxtamembrane domains of the corticotropin releasing factor type I receptor: regulation by G-protein and nonpeptide antagonists.
Peptide ligands bind the CRF(1) receptor by a two-domain mechanism: the ligand's carboxyl-terminal portion binds the receptor's extracellular N-terminal domain (N-domain) and the ligand's amino-terminal portion binds the receptor's juxtamembrane domain (J-domain). Little quantitative information is available regarding this mechanism. Specifically, the microaffinity of the two interactions and their contribution to overall ligand affinity are largely undetermined. Here we measured ligand interaction with N- and J-domains expressed independently, the former (residues 1-118) fused to the activin IIB receptor's membrane-spanning alpha-helix (CRF(1)-N) and the latter comprising residues 110-415 (CRF(1)-J). We also investigated the effect of nonpeptide antagonist and G-protein on ligand affinity for N- and J-domains. Peptide agonist affinity for CRF(1)-N was only 1.1-3.5-fold lower than affinity for the whole receptor (CRF(1)-R), suggesting the N-domain predominantly contributes to peptide agonist affinity. Agonist interaction with CRF(1)-J (potency for stimulating cAMP accumulation) was 12000-1500000-fold weaker than with CRF(1)-R, indicating very weak direct agonist interaction with the J-domain. Nonpeptide antagonist affinity for CRF(1)-J and CRF(1)-R was indistinguishable, indicating the compounds bind predominantly the J-domain. Agonist activation of CRF(1)-J was fully blocked by nonpeptide antagonist, suggesting antagonism results from inhibition of agonist-J-domain interaction. G-protein coupling with CRF(1)-R (forming RG) increased peptide agonist affinity 92-1300-fold, likely resulting from enhanced agonist interaction with the J-domain rather than the N-domain. Nonpeptide antagonists, which bind the J-domain, blocked peptide agonist binding to RG, and binding of peptide antagonists, predominantly to the N-domain, was unaffected by R-G coupling. These findings extend the two-domain model quantitatively and are consistent with a simple equilibrium model of the two-domain mechanism: (1) The N-domain binds peptide agonist with moderate-to-high microaffinity, substantially increasing the local concentration of agonist and so allowing weak agonist-J-domain interaction. (2) Agonist-J-domain interaction is allosterically enhanced by receptor-G-protein interaction and inhibited by nonpeptide antagonist.


Effects of macromolecular transport and stochastic fluctuations on dynamics of genetic regulatory systems.
To predict the dynamics of genetic regulation, it may be necessary to consider macromolecular transport and stochastic fluctuations in macromolecule numbers. Transport can be diffusive or active, and in some cases a time delay might suffice to model active transport. We characterize major differences in the dynamics of model genetic systems when diffusive transport of mRNA and protein was compared with transport modeled as a time delay. Delays allow for history-dependent, non-Markovian responses to stimuli (i.e., "molecular memory"). Diffusion suppresses oscillations, whereas delays tend to create oscillations. When simulating essential elements of circadian oscillators, we found the delay between transcription and translation necessary for oscillations. Stochastic fluctuations tend to destabilize and thereby mask steady states with few molecules. This computational approach, combined with experiments, should provide a fruitful conceptual framework for investigating the function and dynamic properties of genetic regulatory systems.


Developing procedures for students who refuse to care for a client.
The Human Immunodeficiency Virus (HIV) epidemic raised the question of whether students should be required to provide nursing care for clients whose diagnosis for treatments may jeopardize students' health. Policies and procedures are necessary to provide a framework of functioning for faculty and students when students question their patient assignment. The author explains one institution's successful process for developing a procedure which can facilitate development of appropriate policies and procedures by other faculty.


Potential new targets involved in 1,3-dinitrobenzene induced testicular toxicity.
1,3-Dinitrobenzene (DNB) causes testicular injury, particularly to Sertoli cells, and induces apoptosis in the surrounding germinal cells in rodents; however, the mechanisms causing this toxicity are poorly understood. Our studies, using standard and molecular tools, were conducted to better understand the pathogenesis of the testicular effects. Four daily oral doses of 0.1-8mg/kg/day caused marked testicular lesions in rats from 4mg/kg/day. Global transcriptomics revealed cell cycle and cell death as the major biological processes affected with the expression of genes associated with cell cycle progression ("mitotic roles of polo-like kinase") being particularly altered. In a single dose time course study (4mg/kg), no adverse changes were recorded; however, in contrast to the data from the multiple dose study, plasma testosterone and testicular steroidogenesis-related gene expression were affected. These steroid hormone effects were confirmed in vitro using the H295R steroidogenesis assay. With this global approach we show that DNB not only induces apoptosis and interferes with cell cycle in the testes but that DNB can also modulate steroid hormone biosynthesis, suggesting an interference with the endocrine system. However, the contribution of the endocrine changes to the severe testicular lesions is presently unknown and requires further investigation.


The role of the nurse in the medical ward round.
Communication between hospital staff and in-patients, especially regarding the provision of information, has been found to be inadequate although improving information-giving has been demonstrated to have a number of beneficial effects. While the ward round might be a particularly valuable setting for communication, few studies have explored the multidisciplinary nature of rounds. This study obtained the views of 33 consultants, 14 nurses and eight patients and observed three ward rounds in order to determine the nature of present round functioning, and the nurse's role in such a round. The results showed that the rounds studied were not being conducted in a democratic fashion: medical staff dominated and other health care professionals had little involvement. Patients received few explanations and had great difficulty understanding the discussion. The functions nurses were seen to perform involved primarily providing information for medical staff. It is recommended that patients are more involved in rounds and are given more explanations and encouraged to ask questions. Nurses should be educated to assert themselves in ward rounds in order to fulfil roles they prescribe for themselves, and all professionals should aim towards more democratic, equal discussion. There is a need for further research to determine the effectiveness of nurse intervention on patient involvement and satisfaction with the round.


Pupils' evaluation and generation of evidence and explanation in argumentation.
Studies on argument have found that participants tend to prefer explanations to evidence. This apparent bias toward explanation has been qualified recently by research that has found it to diminish with the availability of evidence. This study examines the use of explanation versus evidence in the context of argumentation with reference to the goals of particular argument situations. Seventy-nine eighth-grade pupils at a regular, urban middle school. The pupils read argumentation scenarios, each having the stated goal of either explaining or proving a claim. The pupils rated the degree to which each of two provided assertions (one a theoretical explanation, and the other evidence-based) helped achieve the goal of the argument. On a second task, the pupils chose which of the two assertions should be more effective in achieving the argument goal. On the third task, the pupils generated either an explanation or evidence for each of the argumentation scenarios. Pupils demonstrated sensitivity to the relative epistemic strength of explanation and evidence. They rated explanations as more advantageous in achieving the explanation goal, and evidence as more advantageous in achieving the proof goal. Conversely, however, when asked to generate or recall an explanation or evidence, pupils produced more explanations than evidence independent of the argumentation goal. The study refines the definition of argumentation context to include specific goals. Pupils were sensitive to the context of the argumentation situation (e.g.goals, availability of evidence). However, they appeared to have a disposition toward explanation when asked to produce an explanation or evidence-based justification.


HN protein of Newcastle disease virus causes apoptosis in chicken embryo fibroblast cells.
Newcastle disease virus (NDV), an avian paramyxovirus, induces apoptosis in chicken embryo fibroblast (CEF) cells. In the present investigation, the ability of haemagglutinin-neuraminidase (HN) protein of NDV to cause apoptosis in CEF cells was examined. The results revealed that cells expressing the HN protein demonstrated decreased DNA content, phosphatidylserine exposure and increased cytoplasmic vacuolation. Up-regulation of caspase-1, -9, -8, -3, loss of mitochondrial transmembrane potential and an increase in oxidative stress were also observed in cells expressing the HN protein. Based on the above results it can be concluded that HN protein of NDV causes apoptosis in CEF cells.


Subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care.
The aim of this study was to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care. Cognitive functioning is a critical component for nurses in the assurance of error prevention, identification and correction when caring for patients. Negative changes in nurses' cognitive and psychosocial functioning can adversely affect nursing care and patient outcomes. A descriptive correlational design with stratified random sampling. The sample included 96 nurses from the major geographic regions of the United States. Over 9 months in 2016-2017, data were collected using a web-based survey. Stepwise multiple linear regression analyses were used to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function. Overall, participants reported minimal work function impairment and low levels of subjective cognitive complaints, depression and stress. In multivariate analyses, depression was not associated with nurses' work function. However, perceived stress and subjective concerns about cognitive function were associated with greater impairment of work function. Nurses experiencing subjective cognitive complaints should be encouraged to address personal and environmental factors that are associated with their cognitive status. Additionally, stress reduction in nurses should be a high priority as a potential intervention to promote optimal functioning of nurses providing direct patient care. Healthcare institutions should integrate individual and institutional strategies to reduce factors contributing to workplace stress.


Indications for pylorus preserving gastrectomy for early gastric cancer located in the middle third of the stomach.
Both basic and clinical studies were undertaken to determine the indications for pylorus preserving gastrectomy for patients with early gastric cancer located in the middle third of the stomach. This procedure is different from conventional subtotal gastrectomy in that it retains a 1.5 cm length of the pyloric cuff and it neglects to dissect the suprapyloric lymph node, with the remaining pyloric branch of the vagal nerve being preserved. Therefore, it is essential that this limited operation be performed only in cases without metastasis to the suprapyloric lymph node. The distance from the caudal end of the tumor to the cut edge is far enough when the tumor is in the middle third of the stomach. The direction of lymph flow, as determined in 14 cases by activated carbon particles (CH-40), suggests that there is limited lymph flow towards the suprapyloric lymph node from the middle third of the stomach. Lymph node involvement was investigated in 154 patients with early gastric cancer located in the middle third of the stomach who had undergone conventional subtotal gastrectomy with regional lymph node dissection between 1976 and 1989. By analysis of the relationship between lymph node metastasis and the clinicopathologic findings revealed before operation, i.e. gross appearance, histological classification, and tumor size, the indications for pylorus preserving gastrectomy were determined as follows: (1) any case with tumors smaller than 2.0 cm in maximum length, and (2) cases with a tumor of 2.0 to 4.0 cm if it is a mucosal cancer, if it is located at the greater curvature, or if it is an elevated type IIa cancer. This operation has been performed on 11 patients to date without postoperative complaints or sequelae.


Design, synthesis, and SAR of tachykinin antagonists: modulation of balance in NK(1)/NK(2) receptor antagonist activity.
Through optimization of compounds based on the dual NK(1)/NK(2) antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK(1) and NK(2) potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK(1) potency and thus afforded NK(1) preferential antagonists. Alterations of the piperidine region could then increase NK(2) potency to restore dual NK(1)/NK(2) selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK(1)/NK(2) antagonists, and the third is an NK(1) preferential antagonist. In this paper, the factors affecting the balance of NK(1) and NK(2) selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.


Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality.
The aim of this study was to evaluate and compare brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels as mortality prognosticator and predictor for myocardial dysfunction in severe sepsis and septic shock. Baseline clinical and biological variables were collected from 47 patients with severe sepsis or septic shock. Ventricular systolic function assessed by echocardiography was measured over a 5-day period. Both cTnI and BNP plasmatic levels were determined at intensive care unit (ICU) admission and during the following 15 days. At admission, cTnI and BNP levels were compared to those of 12 control critically ill nonseptic patients. The plasma levels of BNP and cTnI in patients with sepsis were elevated at admission and significantly higher than in the controls. Among patients with sepsis, BNP levels were significantly more elevated in nonsurvivors compared to survivors at admission and 1 day later. The cTnI levels were also significantly more elevated in nonsurvivors compared to survivors, but only at admission. From admission to day 5, patients with sepsis with left ventricular systolic dysfunction had higher BNP plasmatic concentrations than those without; differences were significant at days 3 and 4. In contrast, plasma cTnI levels were similar between the 2 groups. In critically ill patients, sepsis induces significant increase in BNP and cTnI levels. High BNP and cTnI plasma levels during ICU admission appear to be associated with poor outcome of sepsis. Time course of BNP levels seems helpful to discriminate between surviving and nonsurviving patients with sepsis and to detect myocardial dysfunction where troponin levels fail to do so.


Catalytic valorization of starch-rich food waste into hydroxymethylfurfural (HMF): Controlling relative kinetics for high productivity.
This study aimed to maximize the valorization of bread waste, a typical food waste stream, into hydroxymethylfurfural (HMF) by improving our kinetic understanding. The highest HMF yield (30mol%) was achieved using SnCl4 as catalyst, which offered strong derived Brønsted acidity and moderate Lewis acidity. We evaluated the kinetic balance between these acidities to facilitate faster desirable reactions (i.e., hydrolysis, isomerization, and dehydration) relative to undesirable reactions (i.e., rehydration and polymerization). Such catalyst selectivity of SnCl4, AlCl3, and FeCl3 was critical in maximizing HMF yield. Higher temperature made marginal advancement by accelerating the undesirable reactions to a similar extent as the desirable pathways. The polymerization-induced metal-impregnated high-porosity carbon was a possible precursor of biochar-based catalyst, further driving up the economic potential. Preliminary economic analysis indicated a net gain of USD 43-236 per kilogram bread waste considering the thermochemical-conversion cost and chemical-trading revenue.


Assessment of regional lung functional impairment with co-registered respiratory-gated ventilation/perfusion SPET-CT images: initial experiences.
In this study, respiratory-gated ventilation and perfusion single-photon emission tomography (SPET) were used to define regional functional impairment and to obtain reliable co-registration with computed tomography (CT) images in various lung diseases. Using a triple-headed SPET unit and a physiological synchroniser, gated perfusion SPET was performed in a total of 78 patients with different pulmonary diseases, including metastatic nodules (n = 15); in 34 of these patients, it was performed in combination with gated technetium-99m Technegas SPET. Projection data were acquired using 60 stops over 120 degrees for each detector. Gated end-inspiration and ungated images were reconstructed from 1/8 data centered at peak inspiration for each regular respiratory cycle and full respiratory cycle data, respectively. Gated images were registered with tidal inspiration CT images using automated three-dimensional (3D) registration software. Registration mismatch was assessed by measuring 3D distance of the centroid of the nine selected round perfusion-defective nodules. Gated SPET images were completed within 29 min, and increased the number of visible ventilation and perfusion defects by 9.7% and 17.2%, respectively, as compared with ungated images; furthermore, lesion-to-normal lung contrast was significantly higher on gated SPET images. In the nine round perfusion-defective nodules, gated images yielded a significantly better SPET-CT match compared with ungated images (4.9 +/- 3.1 mm vs 19.0 +/- 9.1 mm, P<0.001). The co-registered SPET-CT images allowed accurate perception of the location and extent of each ventilation/perfusion defect on the underlying CT anatomy, and characterised the pathophysiology of the various diseases. By reducing respiratory motion effects and enhancing perfusion/ventilation defect clarity, gated SPET can provide reliable co-registered images with CT images to accurately characterise regional functional impairment in various lung diseases.


Cardiothoracic surgery resident education: update on resident recruitment and job placement.
Applications to cardiothoracic surgery training programs have steadily declined. The application cycle for 2004 marked the first time the number of applicants was lower than the positions offered. This survey reflects on this trend in applications and the perspectives of current and graduating residents. In June 2004, the Thoracic Surgery Residents Association, in conjunction with CTSNet, surveyed residents completing accredited cardiothoracic training or additional subspecialization. Participation was anonymous and voluntary. Of the 140 graduates, 88 responded. Most were male (92%) and married (72%). Their average age was 35.7 years, and 56% had children. The mean educational debt was less than $50,000. Of the 88 respondents, 69 (78%) had plans to seek jobs whereas 15 (17%) sought additional training. Among job-seeking residents, 12% received no offers. Also, 59% of graduates initially sought a position in academics and 41% in private practice. Nearly one quarter (23%) reported that they would not choose a career in cardiothoracic surgery again, and more than half (52%) would not strongly recommend cardiothoracic surgery to potential trainees. Almost all (90%) of the graduates believed that the number of cardiothoracic training spots should be decreased, and 92% believed that a reduction in training positions should be achieved by closing marginal training programs. Additionally, 91% believed reimbursement for cardiothoracic surgery was inadequate, and 88% thought low reimbursement resulted in restricted patient access and decreased quality of care. Cardiothoracic training programs are having difficulty in both applicant recruitment and in suitable job placement. This frustration in the job search coupled with reimbursement and lifestyle issues most likely contributes to the general dissatisfaction conveyed by the graduates. If these trends continue, the field will be faced with a crisis of unfilled residency programs and unemployed graduates.


Compensated pathogenic deviations.
Deleterious or 'disease-associated' mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substituted resulting in disease is the wild-type native residue in the functionally equivalent protein in another species. Such examples are known as 'compensated pathogenic deviations' (CPDs) because, somewhere in the second species, there must be compensatory mutations that allow the protein to function normally despite having a residue which would cause disease in the first species. Depending on the nature of the mutations, compensation can occur in the same protein, or in a different protein with which it interacts. In principle, compensation can be achieved by a single mutation (most probably structurally close to the CPD), or by the cumulative effect of several mutations. Although it is clear that these effects occur in proteins, compensatory mutations are also important in RNA potentially having an impact on disease. As a much simpler molecule, RNA provides an interesting model for understanding mechanisms of compensatory effects, both by looking at naturally occurring RNA molecules and as a means of computational simulation. This review surveys the rather limited literature that has explored these effects. Understanding the nature of CPDs is important in understanding traversal along fitness landscape valleys in evolution. It could also have applications in treating diseases that result from such mutations.


A purine-rich sequence in the human BM-40 gene promoter region is a prerequisite for maximum transcription.
BM-40 (osteonectin, SPARC [secreted protein, acidic, rich in cysteine]) is a highly conserved, matrix-associated protein that is found in basement membranes, bones and remodeling tissues throughout vertebrate evolution. We are reporting the characterization of the 5' end of the human BM-40 gene. Sequence comparison of the 5' region revealed significant homologies with the bovine and murine genes, including a purine-rich stretch composed of two boxes, GGA-box 1 and 2, separated by a pyrimidine-rich spacer element. Transfection analyses of the human BM-40 promoter provide strong evidence that this region comprises several distinct regulatory domains, to which different functions can be assigned. GGA-box 1 is thereby absolutely required and sufficient by itself for maximal BM-40 transcriptional activity, whereas the spacer element has a down-regulatory effect. Comparative transfection analyses in human cell lines, positive or negative for BM-40 transcripts, indicate that the GGA-box sequences in the human promoter, in contrast to the bovine promoter, do not significantly contribute to cell-type specific expression in human cells.


Expression of the Escherichia coli bo-type ubiquinol oxidase with a chimeric subunit II having the CuA-cytochrome c domain from the thermophilic Bacillus caa3-type cytochrome c oxidase.
The C-terminal periplasmic domain of subunit II of the Escherichia coli bo-type ubiquinol oxidase was replaced with the counterpart of the thermophilic Bacillus caa3-type cytochrome c oxidase containing the CuA-cytochrome c domain by means of gene engineering techniques. The chimeric terminal oxidase was expressed by a pBR322 derivative in a terminal oxidase deficient mutant of E. coli, although the amount of the chimeric enzyme was smaller than that of the Escherichia coli bo-type ubiquinol oxidase expressed by the original cytochrome bo-expressing plasmid. The chimeric enzyme showed much higher TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) oxidase activity than the wild-type cytochrome bo, but lower activity than the thermophilic Bacillus caa3-type cytochrome c oxidase. The chimeric subunit II was confirmed to bind to heme C. These results suggest that the CuA-cytochrome c domain grafted to this membrane anchor can facilitate electron transfer from reduced TMPD to low-spin protoheme b in subunit I.


Korean traditional natural herbs and plants as immune enhancing, antidiabetic, chemopreventive, and antioxidative agents: a narrative review and perspective.
The world is becoming increasingly interested in Korean food and its ingredients. The attention goes beyond the typical examples, such as kimchi and fermented sauces; peculiar food ingredients that are widely consumed in Korea are now entering the world's functional food markets. This trend was supported by scientific research, and this review seeks to combine and summarize the findings of the past 10 years. The results are organized into four groups depending on whether the ingredient strengthens the immune system, has antidiabetic effects, has chemopreventive effects, or has an antioxidative effects. We would also like to point out that this review only covers the topic of Korean traditional plants and herbs. After the summary of research findings, we discuss challenges and opportunities, exploring the direction of future research and the potential of Korean traditional food ingredients in food industry and markets.


[X syndrome: does left ventricular myocardial perfusion suffer during exercise?].
Sixteen patients with the X syndrome underwent thallium-201 myocardial scintigraphy. Eleven patients with one-coronary artery disease served as a control group. During bicycle ergometry all the 16 patients showed various degrees of local myocardial perfusion impairments. The foci were located in the basins of various coronary vessels. Impaired myocardial perfusion in patients with the X syndrome was similar to that in patients with moderate, but hemodynamically significant stenosis of a coronary artery. At the same time the impairments were significantly less pronounced than in those with critical stenosis of a coronary artery. Thus, patients with the X syndrome have not only clinical signs of coronary heart disease (anginal episodes), but they also have marked myocardial perfusion impairments during exercise.


Cancer: involvement of replicative origins?
The assumption is made that movable genetic elements related to cancer are replicons and/or replicative origins. Some evidence is provided that certain mobile Alu-origins may represent candidates for precursors of chromosomal insertions. They could incorporate and interact with "fixed" chromosomal origins converting them to "procaryotic" ones. In other words, cancer is considered the result of a short and compact "re-evolution" from eucaryotic to "procaryotic" replication units.


NNWarp: Neural Network-based Nonlinear Deformation.
NNWarp is a highly re-usable and efficient neural network (NN) based nonlinear deformable simulation framework. Unlike other machine learning applications such as image recognition, where different inputs have a uniform and consistent format (e.g. an array of all the pixels in an image), the input for deformable simulation is quite variable, high-dimensional, and parametrization-unfriendly. Consequently, even though the neural network is known for its rich expressivity of nonlinear functions, directly using an NN to reconstruct the force-displacement relation for general deformable simulation is nearly impossible. NNWarp obviates this difficulty by partially restoring the force-displacement relation via warping the nodal displacement simulated using a simplistic constitutive model - the linear elasticity. In other words, NNWarp yields an incremental displacement fix per mesh node based on a simplified (therefore incorrect) simulation result other than synthesizing the unknown displacement directly. We introduce a compact yet effective feature vector including geodesic, potential and digression to sort training pairs of per-node linear and nonlinear displacement. NNWarp is robust under different model shapes and tessellations. With the assistance of deformation substructuring, one NN training is able to handle a wide range of 3D models of various geometries. Thanks to the linear elasticity and its constant system matrix, the underlying simulator only needs to perform one pre-factorized matrix solve at each time step, which allows NNWarp to simulate large models in real time.


Personal crisis: growth or pathology?
The aim of this article is to present an emerging theoretical framework for viewing certain types of personal crises as developmentally healthy rather than as psychopathological. These types of crises are referred to as "spiritual emergence" and "spiritual emergency." Selected literature from psychology, psychiatry, and philosophy is used to describe the new paradigm, which views the development of human consciousness across the life span as going beyond the well-adjusted and productive adult ego. The intent is to introduce this paradigm and some of its implications for further critical consideration by health promotion professionals. It is not the authors' purpose to critically evaluate the relevant theoretical literature in this article. The new paradigm represents an expanded theory of human development that explicitly recognizes a spiritual dimension in personal growth and health. Within this paradigm, spiritual emergence and spiritual emergency are viewed as signs of transitional, personal growth rather than as symptoms of psychopathology. Accordingly, signs of growth need to be differentiated from symptoms of pathology. The first step in doing this is to contextualize human experience in a larger developmental framework. Health promotion professionals may benefit personally and professionally by being aware of the new developmental paradigm which differentiates spiritual growth from pathological symptoms. Further theoretical clarification and research will be needed before detailed recommendations for practice can be made.


Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [18F]DOPA PET and fMRI study.
Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine. Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans. No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups. The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.


Using Pyridinium Styryl Dyes as the Standards of Time-Resolved Instrument Response.
In this paper, two pyridinium styryl dyes, [2-(4-dimethylamino-phenyl)-vinyl]-1-methylpyridinium iodide (DASPMI), were synthesized and characterized by steady state fluorescence spectroscopy as well as picosecond and femtosecond time-resolved fluorescence spectroscopies. Both dyes exhibit large Stokes shifts and fluorescence decays equivalent to the instrument response function (IRF) standards employed in time-correlated single-photon counting. Due to their styryl and pyridinium moieties, DASPMIs have higher peak fluorescence intensity and shorter excited-state lifetimes than iodide ion-quenched fluorophores. The fluorescence lifetimes of o-DASPMI and p-DASPMI were measured to be 6.6 ps and 12.4 ps, respectively. The fluorescence transients of these DASPMIs were used as the IRFs for iterative reconvolution fitting of the time-resolved fluorescence decay profiles of Rhodamine B (RhB), sulforhodamine B (SRB), and the SRB-SRB2m RNA aptamer complex. The quality of the fits employing the DASPMI-derived IRFs are consistently equivalent to those employing IRFs obtained from light scattering. These results indicate that DASPMI-derived IRFs may be suited for a broad range of applications in time-resolved spectroscopy and fluorescence lifetime imaging microscopy (FLIM), especially in the visible emission range.


Association of HLA-DQB1*0201 with stiff-man syndrome.
Stiff-man syndrome (SMS) is a rare disorder of the central nervous system of probable autoimmune origin. Patients with SMS often have other autoimmune diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM). Approximately 60% of patients with SMS have high titers of autoantibodies against the enzyme glutamic acid decarboxylase. Similar to SMS, the majority of patients with IDDM have autoantibodies against glutamic acid decarboxylase at or before diabetes onset, although usually at a lower titer and with a different reaction pattern than patients with SMS. To investigate the immunogenetic basis of SMS, we HLA-typed 18 patients with the disease. Seventy-two percent carried the DQB1*0201 allele (13 of 18, P = 0.02 vs. 18 of 48 controls), indicating that SMS is associated with this allele. DQB1*0201 is also a susceptibility allele for IDDM and other autoimmune diseases. Patients with SMS carried the IDDM-protective DQB1*0602 allele and other sequence-related DQB1*06 alleles with the same frequency observed in controls. In contrast, these alleles are rarely found in IDDM. Five of 8 (62.5%) SMS patients lacking a DQB1*06 allele were diabetic in contrast to only 2 of 10 (20%) with a DQB1*06 allele (P = 0.08), suggesting that the presence of DQB1*0602 or other DQB1*06 alleles may be associated with a reduced prevalence of diabetes among patients with SMS.


Pharmacokinetics of oral omeprazole in llamas.
Gastrogard, an oral formulation of omeprazole, was given to six llamas at a dose of 4 mg/kg once a day for 6 days. Plasma samples were collected at 0, 15, 30, 45, and 60 min and 2, 3, 4, 6, 8, 12, and 24 h on days 1 and 6. Plasma omeprazole concentrations were measured by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters calculated included the area under the curve (AUC(0-infinity)), peak plasma concentration (Cmax), time of peak plasma concentration (Tmax), and terminal half-life (t(1/2)). On day 6, plasma omeprazole concentrations reached a Cmax of 0.12 microg/mL at a Tmax of 45 min. The t(1/2) of omeprazole was 2.3 h and the AUC(0-infinity) was 0.38 h x microg/mL. Plasma concentrations remained above the minimum concentration for inhibition of gastric acid secretion projected from other studies on day 6 in all the llamas for approximately 6 h. However, the AUC(0-infinity) was below the concentrations associated with clinical efficacy. It was not possible to measure oral systemic bioavailability because there was no i.v. data collected from these animals. However, using data published on the i.v. pharmacokinetics of omeprazole in llamas, oral absorption was estimated to be only 2.95%. Due to low absorption the oral dose was increased to 8 and 12 mg/kg and studies were repeated. There were no significant differences in Cmax, Tmax, or AUC(0-infinity) for either of the increased doses. These results indicate that after 6 days of treatment with doses up to 12 mg/kg, oral omeprazole produced plasma drug concentrations which are not likely to be associated with clinical efficacy in camelids.


Problem-based learning outcomes: the glass half-full.
To compare the characteristics and outcome data of students from a single institution with a two-track, problem based learning (PBL) and standard (STND) curriculum. PBL and STND students from nine graduating classes at Southern Illinois University School of Medicine were compared using common medical school performance outcomes (USMLE Step 1, USMLE Step 2, clerkship mean ratings, number of clerkship honors and remediation designations, and the senior clinical competency exam), as well as common admission and demographic variables. PBL students were older, and the cohort had a higher proportion of women. The two tracks had similar USMLE Step 1 and 2 mean scores and pass rates. Performance differences were significant for PBL students in two clerkships as well as in the clerkship subcategories of clinical performance, knowledge and clinical reasoning, and noncognitive behaviors. In addition, the proportion of PBL students earning honors was greater. The traditional undergraduate educational outcomes for the PBL and STND students are very positive. In several of the clerkship performance measures, the PBL students performed significantly better, and in no circumstance did they perform worse than the STND students.


Spasmolytic and antinociceptive activities of ursolic acid and acacetin identified in Agastache mexicana.
Agastache mexicana is a plant in high demand that has long been used in Mexican folk medicine to treat anxiety, insomnia, and stomachache, among other afflictions. Ursolic acid and acacetin were isolated and identified as two possible active compounds of A. mexicana aerial parts. An antinociceptive response was demonstrated in a significant and dose-dependent manner with ursolic acid and acacetin (i. p. and p. o.) in comparison to the analgesic diclofenac by using the writhing test in mice. Moreover, acacetin also produced a significant concentration-dependent spasmolytic response with major efficacy compared to ursolic acid and papaverine by using rings from the isolated guinea pig ileum. These results provide evidence of the presence of two active constituents of Agastache mexicana reinforcing its utility as a therapy for visceral pain as used in traditional medicine.


[123I/125I]-Ro 43-0463, a site specific tracer for MAO-B mapping with autoradiography as well as with SPET.
The compound Ro 43-0463 [N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide)] is the iodo-analogue of Lazabemid (Ro 19-6327). The latter is well known to bind site specifically with KD = 15.7 nmol/l to the enzyme monoamine oxidase type B (MAO-B) which it inhibits (IC50 = 2 *10(-8) mol/l) time dependently and reversibly. Ro 43-0463 having an IC50 of 3*10(-8) mol/l was labelled with 123I as well as with 125I to get a tool for measuring the MAO-B distribution autoradiographically and in the human brain with SPET (Single Photon Emission Tomography). The halogen exchange reaction of the bromo-precursor (Ro 18-4950) in the presence of CuSO4 and ascorbic acid was applied. The reaction conditions were optimized, varying the parameters time (30 to 105 min), precursor concentration (1 to 3.5 mg) and temperature (130 to 200 degrees C). The purification of [123I/125I]-Ro 43-0463 was performed on HPLC (Lichrosorb RP-18, 5 mu m, 250 x 8 mm) with 0.36 M H3PO4/EtOH 97/3 and 0.01 M (NH4)2HPO4 (1.5 ml/min) as eluent. The labelling yield was found to range between 60 and 70%. The activity concentration ranged between 18.5 and 37 MBq/ml. Autoradiography with rat brain slices was performed using 5 nM [125I]-Ro 43-0463 in TRIS-buffer (pH 7.4) for 90 min at 20 degrees C. It showed a radioactivity pattern corresponding to the known distribution of MAO-B in the rat brain and proved, after displacement with L-Deprenyl (1 mu M), the high specificity of binding Ro 43-0463.


Postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery.
To compare 4 analgesic protocols in dogs undergoing stifle joint surgery. Randomized, blinded, prospective clinical trial. Animals-48 client-owned dogs that underwent stifle joint surgery. Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of a combination of morphine, lidocaine, and ketamine; a lumbosacral epidural with morphine and ropivacaine; both treatments (ie, constant rate infusion and lumbosacral epidural); or only IM premedication with morphine. Indices of cardiorespiratory function and isoflurane requirement were recorded at 5-minute intervals during anesthesia. A validated sedation scoring system and the modified Glasgow composite measure pain score were used to assess comfort and sedation after surgery and anesthesia once the swallowing reflex returned and a body temperature of ≥ 36.7°C (98.1°F) was attained. Pain and sedation scores were acquired at 60-minute intervals for 4 hours, then at 4-hour intervals for 24 hours. Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia. No differences in heart rate, respiratory rate, systolic arterial blood pressure, end-tidal Pco2, end-tidal isoflurane concentration, and vaporizer setting were detected among groups. No differences in pain score, sedation score, rescue analgesia requirement, or time to first rescue analgesia after surgery were detected. Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.


Nurse leaders and competition--are the blind leading the blind to market?
Marketisation of health care provision in the UK will result in a 'seismic' culture shift for many organizations and their nurse leaders. This short item explores the role nurse leaders will need to play in a world where increasingly, competition is becoming as important as collaboration.


Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review.
This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease. CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control. Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.


Multiloculated pyogenic brain abscess: experience in 25 patients.
To report our experience in treating multiloculated pyogenic brain abscess and determine whether there are differences in the bacteriology, predisposing factors, treatment choices, and outcomes between multiloculated and uniloculated brain abscesses. We studied clinical data collected during a 16-year period from 124 patients with pyogenic brain abscess, including 25 cases of multiloculated abscess. The incidence of multiloculated brain abscess was 20%. In these 25 patients, hematogenous spread from a remote infectious focus was the most common cause of infection, as it was for the cases of uniloculated abscess. Headache and hemiparesis were the most common symptoms in patients with multiloculated abscess. In patients with uniloculated abscess, fever was the most common symptom. Viridans streptococci were the most commonly isolated pathogens. Bacteroides fragilis was the most common anaerobe in multiloculated abscess, and aerobic gram-negative bacilli were the most common pathogens in patients with uniloculated abscess. Of the patients with multiloculated abscess, 21 were treated surgically and 4 were treated with antibiotics only. Overall, eight patients (38%) needed another operation because of abscess recurrence after the initial operation. In uniloculated abscess, the rate of abscess recurrence after initial surgery was 13.1%. Mortality was 16% in multiloculated abscess and 17.1% in uniloculated abscess. Multiloculated abscesses accounted for 20% of our patients with pyogenic brain abscess. Excision seems to be the more appropriate surgical choice in multiloculated abscess. Prognosis for patients with multiloculated abscess can be as good as that for patients with uniloculated abscess. However, clinicians must carefully monitor these patients because the possibility of recurrence after surgery is significantly higher in patients with multiloculated abscess than in those with uniloculated abscess.


Differences in the amyloid-beta-induced inflammatory response in microglia from C57BL/6 and A/J strains of mice.
The microglial inflammatory response to Abeta(1-42) stimulation with or without IFN-gamma priming was investigated in low and high responder strains of mice, A/J and C57BL/6, respectively. A/J microglia showed moderate morphological changes upon stimulation with IFN-gamma alone or with Abeta(1-42). Conversely, C57BL/6 microglia showed major changes in their cellular morphology, which were accompanied by a decrease in NO release and a marked increase in TNF-alpha production. These results indicate that the magnitude of the microglial inflammatory response to Abeta is strongly influenced by genetic factors. Individual differences in the regulation of the microglial response may be a key player in the rate of development of the neuropathology of AD.


In vitro comparison of the effects of two forms of hydroxyethyl starch solutions on platelet function in dogs.
To evaluate the effect of 2 hydroxyethyl starch (HES) preparations (ie, HES solution with a molecular weight of 600 kd and a degree of substitution of 0.7 [HES 600/0.7] and a calcium-containing polyionic HES solution with a molecular weight of 670 kd and a degree of substitution of 0.75 [HES 670/0.75]) on canine platelet function. Blood samples from 10 healthy adult dogs. Dilution of citrated whole blood was performed with saline (0.9% NaCl) solution, HES 600/0.7, and HES 670/0.75 at ratios of 1:9 (ie, 1 part saline solution or colloid to 9 parts whole blood) and 1:3. Measurements of time to platelet plug formation in a capillary tube (ie, closure time) were made by use of a bench-top platelet function analyzer with collagen and ADP platelet agonists. Mean baseline closure time was 68.0 +/- 15.3 seconds. A 1:3 dilution of whole blood with saline solution, HES 600/0.7, and HES 670/0.75 resulted in mean closure times of 85.8 +/- 15.7 seconds, 100.6 +/- 18.6 seconds, and 101.6 +/- 16.2 seconds, respectively. Closure time following 1:3 dilution of whole blood with saline solution was significantly different from baseline and from 1:9 dilution with saline solution. Closure time following 1:3 dilution of whole blood with HES 670/0.75 was significantly different from baseline, 1:3 and 1:9 dilutions with saline solution, and 1:9 dilutions with HES 600/0.7 or HES 670/0.75. Saline solution, HES 600/0.7, and HES 670/0.75 affect canine platelet function by prolonging closure times; HES solutions prolonged closure time to a greater extent than saline solution.


The automated counting of beating rates in individual cultured heart cells.
The effect of drugs on the beating rate of cultured heart cells can be monitored in a number of ways. The simultaneous automated measurement of beating rates of a number of cells allows drug effects to be rapidly quantified. A photoresistive detector placed on a television image of a cell, when coupled to operational amplifiers, gives binary signals that can be processed by a microprocessor. On this basis, we have devised a system that is capable of simultaneously monitoring the individual beating of six single cultured heart cells. A microprocessor automatically processes data obtained under different experimental conditions and records it in suitable descriptive formats such as dose-response curves and double reciprocal plots.


Drug-induced endothelial injury potentiates lung colonization in a murine fibrosarcoma model.
Lung colonization induced by the intravenous injection of fibrosarcoma cells into syngeneic mice was enhanced by the pretreatment of mice with cyclophosphamide (CPA), adriamycin (ADM), cis-diammine-dichloroplatinum II (DDP) and methotrexate (MTX). At equitoxic levels, CPA showed greater enhancement of the lung colonization than the other drugs treated. After a two-hour pretreatment of an endothelial monolayer culture, the adhesion of fibrosarcoma cells to endothelial cells was enhanced by all drugs, and the greatest enhancement was obtained with CPA. Data from these experiments supports the hypothesis that endothelial cell damag by anticancer drugs may facilitate metastasis of circulating tumor cells.


Muscle biopsy studies on protein-energy malnutrition in patients with chronic relapsing pancreatitis.
Malnutrition is a common finding in chronic pancreatitis and its pathogenesis is multifactorial. In 14 patients with chronic pancreatitis we assessed the dietary intake, some anthropometric indices and the concentration of some serum proteins. In muscle specimens obtained by needle biopsy we examined the DNA, RNA and non-collagen alkali-soluble protein (ASP) content. In muscle we determined also the activity of cathepsin D, an enzyme involved in intracellular myofibrillar catabolism. Protein and energy intake were lower than in the normal healthy population. Plasma protein content (an index of liver protein synthesis) was generally in the normal range, whereas anthropometry and the biochemical muscle indices were generally subnormal, suggesting a depressed muscle protein content and synthesis (evaluated, respectively, by the ASP: DNA and RNA: DNA ratios). Cathepsin D activity was lower than in controls, and the percentage of 'free' activity tended to be higher but not significantly. This study suggests that muscle protein content and synthesis are reduced in patients with chronic pancreatitis, whereas liver protein synthesis is generally preserved. Possibly as a consequence of metabolic abnormalities and/or of an inadequate protein and energy intake, the nutritional status was often abnormal in our patients and a nutritional support therapy was needed.


Observation of the highly organized development of granule cells in rat cerebellar organotypic cultures.
Cerebellar slices of 9-day-old rats were cultured for a week at the interface between air and a culture medium containing horse serum and hormone cocktail, and the development of granule cells was characterized morphologically. The typical layered structure of the cerebellar cortex was well preserved during the cultivation. Many granule cells in the external granular layer (EGL) proliferated actively within the early culture period. They were migrating downward at 3 days in vitro (DIV) and almost completed the migration to the internal granular layer (IGL) after 6 DIV. In the middle and upper molecular layer (ML), parallel fibers were elongated horizontally, which is the orientation 90 degrees rotated compared to that in vivo. They formed synapses with Purkinje cell dendrites. Regional differences in synapse density and maturity existed which might reflect a gradient in progressive synapse formation comparable to that in vivo. Thus, a serial process of highly organized development of granule cells was realized for the first time in vitro, although some spatial or temporal modifications existed. Such a culture system could be a useful experimental model for the study of cellular and molecular mechanisms of spatiotemporally organized neuronal development.


Electron microscopic cytochemistry of cytochrome oxidase activity in the conduction system of the canine heart.
Histochemistry and electron microscopic cytochemistry of cytochrome oxidase in the conduction system were studied with the 3,3'-diaminobenzidine (DAB) method in adult canine hearts. This enzyme was distinctly less active in the entire conduction system than in the working myocardium. By electron microscopy, enzymatic activity per cristal membrane was apparently similar in both specialized and working cardiocytes. However, the volume fraction of cell occupied by mitochondria and the density of cristal membranes in mitochondria were smaller in the specialized cells in the sinus node, atrioventricular (AV) node, His bundle, and Purkinje fibers. These observations define the nature of decreased histochemical activity of cytochrome oxidase in cells of the conduction system, which is caused entirely by the decrease in activity per unit of mitochondrial volume and unit of cell volume in the specialized cardiac tissues.


Dot immunogold filtration assay (DIGFA) with multiple native antigens for rapid serodiagnosis of human cystic and alveolar echinococcosis.
A new 3-min rapid dot immunogold filtration assay (DIGFA) for serodiagnosis of human cystic and alveolar echinococcosis was developed using four native antigen preparations: crude and partially purified hydatid cyst fluid extracts from Echinococcus granulosus (EgCF and AgB), E. granulosus protoscolex extract (EgP) and Echinococcus multilocularis metacestode antigen (Em2). The overall sensitivity of DIGFA in a hospital diagnostic setting was 80.7% for human cystic echinococcosis (CE) (n=857) and 92.9% for human alveolar echinococcosis (AE) (n=42). Highest specificity was 93.4% with AgB extract for CE, and 90.3% with Em2 antigen for AE when CE versus AE cross-reactivity was excluded. Anti-AgB antibodies were present in 35.5% of AE cases and anti-Em2 in 7.4% of CE cases. In endemic communities in northwest China screened for echinococcosis, the sensitivity of DIGFA ranged from 71.8% to 90.7% in comparison to abdominal ultrasound; specificity for CE using AgB was 94.6% and for AE using Em2 was 97.1%. This simple eye-read rapid test can be used for both clinical diagnostic support, as well as in conjunction with ultrasound for mass screening in endemic CE and AE areas.


A survey of prescribing practices for monoamine oxidase inhibitors.
A survey examined prescribing practices for monoamine oxidase inhibitors (MAOIs) and explored reasons for the widely noted decline in their use. A one-page questionnaire was sent in 1997 to 1,129 members of the Michigan Psychiatric Association. A total of 717 responses were received, for a response rate of 64 percent. Only data from the 573 psychiatrists who were currently practicing were used. Twelve percent of the respondents never prescribed MAOIs, 27 percent had not prescribed them for at least three years, and 17 percent had prescribed them from one to three years ago. Thirty percent of the respondents had prescribed an MAOI within the past three months, and 14 percent between three and 12 months ago. The most frequent reasons for not prescribing the drugs were side effects and interactions with other medications (46 percent), preference for other medications (30 percent), and dietary restrictions necessary for patients taking MAOIs (19 percent). Ninety-two percent of respondents believed that MAOIs were useful for atypical depression, 64 percent for major depression, 54 percent for melancholic depression, 56 percent for panic disorder, 44 percent for social phobia, 27 percent for dysthymia, 12 percent for obsessive-compulsive disorder, and 19 percent for posttraumatic stress disorder. However, only 2 percent said they would use MAOIs as their first-line treatment in atypical depression, and only 3 percent would use them a first-line treatment in social phobia. The results document the commonly held view that practicing psychiatrists believe MAOIs are efficacious but use them infrequently, primarily due to concerns about side effects and drug interactions.


[Bimodal evoked potentials during long-term therapy with conventional or slow release preparations of carbamazepine and valproic acid in children and adolescents with epilepsy].
The measurement of evoked potentials (EPs) may be particularly useful in clinical neuropharmacology for investigation of drug effects of afferent nerve conduction within CNS. The study aims at estimating the long term effects of conventional or slow release formulation (CR) of carbamazepine (CBZ) and valproid acid (VPA) on visual (VPA) and brainstem auditory (BAEP) evoked potentials. Investigation covered 125 patients 8 to 18 years old to whom both formulations of CBZ or VPA were administered in monotherapy. Everyone received a drug dosage which gave an adequate therapeutic plasma concentration and satisfactory seizure control. Antiepileptic drugs (AEDs) plasma levels were measured by means of fluorescence polarization immunoassay method aided of TDx Analyzer (Abbott, Diagnostic). EPs were registered by means of Multiliner (Toennies, Germany). A pattern of reversal stimulation for VEP was used. The latencies of N75, P100, N145 as well as interpeak amplitudes of N75/P100, P100/N145 were evaluated. The following BAEP parameters were considered: morphology of the potential, absolute latencies of waves I, III, V and I-III, III-V, I-V. EP were always performed in the same conditions and with the same equipment for the epileptic and control groups. The obtained values were compared with age-matched control group. The following BAEP abnormalities were observed: prolonged absolute latencies of waves I, III, V as well as prolonged IPLs I-III. The BAEP V/I amplitude ratio and morphology of the waves were normal in all patients. The VEPs abnormalities manifested as prolongation of P100 or N145 latencies and reduction of amplitudes N75/P100, P100/N145. Results of these electrophysiological studies with CBZ and VPA demonstrate that EP are sensitive, noninvasive reflectors of AEDs effects within the CNS.


Accreditation in Primary Health: RACGP Standards for General Practice.
General Practitioners play a crucial role as "gate-keepers" to the health system. In this context, they have a profound influence on both health outcomes and health expenditure. Since the introduction in 1999 of a formal, peer-driven external accreditation process, over 4,590 Australian general practices have achieved full accreditation. The process of re-ccreditation has commenced, subsequent to a review of the original standards, and with an ongoing focus on continuous quality improvement. This article describes a typical accreditation survey visit, and explains the accreditation criteria and how they are reviewed by the surveyors. There is discussion also of the impact of this new accreditation system on general practice.


Dedicated breast computed tomography: Basic aspects.
X-ray mammography of the compressed breast is well recognized as the "gold standard" for early detection of breast cancer, but its performance is not ideal. One limitation of screening mammography is tissue superposition, particularly for dense breasts. Since 2001, several research groups in the USA and in the European Union have developed computed tomography (CT) systems with digital detector technology dedicated to x-ray imaging of the uncompressed breast (breast CT or BCT) for breast cancer screening and diagnosis. This CT technology--tracing back to initial studies in the 1970s--allows some of the limitations of mammography to be overcome, keeping the levels of radiation dose to the radiosensitive breast glandular tissue similar to that of two-view mammography for the same breast size and composition. This paper presents an evaluation of the research efforts carried out in the invention, development, and improvement of BCT with dedicated scanners with state-of-the-art technology, including initial steps toward commercialization, after more than a decade of R&D in the laboratory and/or in the clinic. The intended focus here is on the technological/engineering aspects of BCT and on outlining advantages and limitations as reported in the related literature. Prospects for future research in this field are discussed.


Incidence and predictors of early complications following primary and revision total ankle arthroplasty.
Total ankle arthroplasty (TAA) offers an effective option for end-stage osteoarthritis. The incidence and preoperative risk factors for early adverse events (AEs) following primary and revision TAA may be useful information for providers. A large database was queried from 2010 to 2016 to identify 905 patients of whom 818 underwent primary TAA (90.4%) and 87 underwent revision TAA (9.6%). Data on patient demographics, comorbidities, and hospital length of stay were analyzed as risk factors for reported 30-day AEs. The overall AE rate was 5.5% (50/905) for the entire cohort. AEs occurred more frequently for revision TAA (9/87) than primary TAA (41/818) cases (OR 2.43, p=0.022). Age (OR 1.03, p=0.045), BMI (OR 1.04, p=0.046), and revision TAA (OR 2.56, p=0.002) were independent risk factors for 30-day AEs in multivariate analysis. Older age, higher BMI, and revision cases are associated with a higher risk of AEs.


Learning theory and its application to the use of social media in medical education.
There is rapidly increasing pressure to employ social media in medical education, but a review of the literature demonstrates that its value and role are uncertain. To determine if medical educators have a conceptual framework that informs their use of social media and whether this framework can be mapped to learning theory. Thirty-six participants engaged in an iterative, consensus building process that identified their conceptual framework and determined if it aligned with one or more learning theories. The results show that the use of social media by the participants could be traced to two dominant theories-Connectivism and Constructivism. They also suggest that many medical educators may not be fully informed of these theories. Medical educators' use of social media can be traced to learning theories, but these theories may not be explicitly utilised in instructional design. It is recommended that formal education (faculty development) around learning theory would further enhance the use of social media in medical education.


Prospective comparison of indwelling cannulas drain and needle aspiration for symptomatic seroma after mastectomy in breast cancer patients.
Postoperative seroma is the most frequent sequelae after mastectomy and axillary surgery with no optimal regimens for seroma resolution recommended in routine clinical. Indwelling cannulas with needle and catheter have been widely used in long-term medication therapies, but evidence of indwelling cannulas in seroma management after mastectomy is lacking. The purpose of this study is to evaluate the feasibility of indwelling cannulas in seroma management after mastectomy. Patients who underwent modified radical mastectomy (MRM) and developed symptomatic seroma after removal of the drains between August 2017 and December 2018, were randomized into two groups either indwelling cannulas drain of seroma (Group A) or needle aspiration of seroma (Group B). We prospectively compared the number of visits for seroma, the time from removal of the drain to the final seroma resolution and the cost between the methods. A total of 860 patients underwent MRM between August 2017 and December 2018, among which 86 patients who developed symptomatic seroma after removal of the drains, were randomized into two groups either Group A or Group B. The number of visits for seroma in Group A was 2.35 ± 0.69 times, which was less than those in Group B (4.86 ± 1.06 times). Similarly, the time of drain removal to final seroma resolution in Group A was 4.65 ± 0.78 days, which was shorter than 7.09 ± 1.54 in Group B. In Group A, the total mean cost per patient (25.81 ± 7.71 RMB) was less than the total mean cost per patient (49.30 ± 9.85 RMB) in Group B. Cost savings were noted with using indwelling cannulas in seroma management. It is feasible to drain indwelling cannulas drain for postmastectomy seroma, with less visits for patients, rapid seroma resolution and less cost. Indwelling cannulas can be an efficient, cost effective solution to treat symptomatic seroma after breast surgery.


What do medical students know about childhood asthma?
A questionnaire designed to measure knowledge about childhood asthma was completed by 216 of the 311 (69%) undergraduate medical students at the University of Newcastle. First year students had a mean score of 16.2 (maximum possible score was 31) which was similar to the background community score of 13.0 obtained in a group of parents with no close contact with asthma. Knowledge about asthma increased over each of the 5 years of the medical course. Final-year students had a mean score of 28.7 (range: 25-31) which was similar to a group of parents thought by their paediatricians to have a high level of knowledge about asthma (mean: 25.3, range: 18-31). The progression of knowledge over the 5 years of the course provided interesting information about the learning process. Although second year students completed the questionnaire after a term devoted to coursework in respiratory medicine, only 26% were able to name two preventive agents and 21% named three agents useful during acute attacks of asthma. Third year students gave correct responses in 39 and 45% of cases, respectively, and the correct response rates rose to 78 and 97% in the fifth year. This was probably because the theoretical knowledge needed to be acquired and tested against a clinical scenario before it could be used. The study demonstrated an increase in knowledge about asthma throughout the problem-based medical course. In addition to providing information about the educational process, it provided information about the questionnaire which was able to measure a range of knowledge and not just extremes of asthma knowledge.


Salvage of poorly developed arteriovenous fistulae with percutaneous ligation of accessory veins.
Many arteriovenous (AV) fistulae fail to achieve an adequate blood flow or size for successful cannulation because of accessory veins. We describe a simple technique to ligate accessory veins that does not require a surgical incision. In this retrospective study, 17 end-stage renal disease patients underwent ligation of accessory veins of poorly developed AV fistulae. There were 14 men and 3 women, and their average age was 50 +/- 13 years. There were 14 radiocephalic and 3 brachiocephalic fistulae. After identifying accessory veins with a fistulogram, two nonabsorbable 2-0 polypropylene (Prolene) sutures were placed percutaneously around each accessory vein in proximity to the AV fistula. Successful ligation was confirmed with a repeat fistulogram. This procedure was undertaken after 4 +/- 3 months following surgical placement. Successful maturation was defined as adequate blood flow to support effective hemodialysis and adequate caliber to allow for repeated cannulation with a 15G or 16G needle. Of 17 AV fistulae, 15 (88%) successfully matured 1.7 +/- 1 month (range, 0.3 to 6 months) after the procedure. The average number of accessory veins ligated was 1.7 +/- 0.8 (range, 1 to 3). All AV fistulae that matured after ligation of accessory veins were functioning at 44.5 +/- 12 weeks after first use. A technique for salvaging nonmaturing AV fistulae not requiring surgical cutdown for ligation of accessory veins is described. AV fistulae mature quickly after ligation of accessory veins. This is a rapid and safe procedure that can increase the prevalence of AV fistulae.


The Usefulness of Virtual Fluoroscopic Preprocedural Planning During Percutaneous Transhepatic Biliary Drainage.
To retrospectively evaluate the usefulness of virtual fluoroscopic preprocedural planning (VFPP) in the percutaneous transhepatic biliary drainage (PTBD) procedure. Twenty-two patients who were treated by PTBD were included in this study. Twelve patients were treated using PTBD intraoperative referencing coronal computed tomography (CT) images (i.e., coronal CT group), and ten patients were treated using PTBD intraoperative referencing VFPP images (i.e., VFPP group). To analyze the effect of the intraoperative referencing VFPP image, the VFPP group was retrospectively compared with the coronal CT group. The characteristics of both patient groups were not statistically significantly different. There were no significant differences in the targeted bile duct, diameter and depth of the target bile, breath-holding ability, number of targeted bile duct puncture attempts, change in the targeted bile duct, and exchange of the drainage catheter. However, the X-ray fluoroscopy time and the procedure time were significantly shorter in the VFPP group than in the coronal CT group (196 vs. 334 s, P < 0.05; and 16.0 vs. 27.2 min, P < 0.05). Intraoperative referencing using the VFPP imaging in PTBD intuitively can be a useful tool for better localization of the guidewire in the bile duct and thereby shorten the X-ray fluoroscopy time and procedure time while minimizing radiation exposure and complications.


The usefulness of a prenatal genetic questionnaire in genetic risk assessment.
To evaluate a prenatal questionnaire as a genetic screen and as an aid in pre-amniocentesis genetic risk assessment. In a retrospective cohort study, charts were reviewed for 158 consecutive women of advanced maternal age referred for genetic counseling. Genetic risks identified by use of a questionnaire completed by 79 consecutive patients were compared with those risks identified by the referring physician, those identified during subsequent three-generation pedigree analysis, and to genetic risks identified by pedigree evaluation of 79 consecutive individuals who underwent genetic counseling without the aid of a questionnaire (controls). Sixteen (20%) of the questionnaires revealed a previously unidentified genetic risk. The sensitivity and specificity of the questionnaire were determined to be 40.0 and 97.4%, respectively. Pedigree analysis alone (control group) identified significantly more at-risk pedigrees than did the questionnaire alone (34 versus 20%, P < .05), but identified significantly fewer at-risk pedigrees than obtained from the study group patients who completed a questionnaire and pedigree evaluation (34 versus 50.6%, P < .05). Of all 158 patients, 15.2% (n = 24) underwent additional testing on the basis of genetic risk assessment. There was no difference between the study and control groups in additional evaluations performed (P = 1.0). A three-generation pedigree is superior to a questionnaire in genetic risk assessment. The questionnaire was not sufficiently sensitive to serve independently as an adequate genetic screen or risk assessment tool and did not influence subsequent fetal evaluation. Assessment of the sensitivity and specificity of prenatal genetic questionnaires should be undertaken before their routine clinical use.


Porcine embryonic brain cell cytotoxicity mediated by human natural killer cells.
Intracerebral transplantation of porcine embryonic dopamine-producing neurons has been suggested as a method to treat patients with Parkinson's disease. Even though the brain is an immunologically privileged site, neuronal xenografts are usually rejected within a few weeks. T cells are important for this process, but the exact cellular events leading to rejection are poorly characterized. Brain cells from ventral mesencephalon of 26-27-day-old pig embryos were used as target cells in flow cytometry-assessed cytotoxicity assays using non- and IL-2-activated CD3- CD16+ CD56+ human natural killer (NK) cells as effector cells. The ability of human NK cells to kill pig embryonic brain cells by antibody-dependent cellular cytotoxicity (ADCC) in the presence of nondepleted and anti-Gal alpha1,3Gal antibody-depleted human blood group AB serum (AB serum) was evaluated using the same assay. Both nondepleted and anti-Gal alpha1,3Gal antibody-depleted AB serum could mediate ADCC of pig embryonic VM cells when human NK cells were used as effector cells. Nonactivated NK cells did not show any direct cytotoxic effect on freshly isolated VM cells, whereas IL-2-activated NK cells killed approximately 50% of the VM cells at an effector-to-target ratio of 50:1 in a 4-h cytotoxicity assay. Activation of VM cells by TNF-alpha did not change their sensitivity to human NK cell cytotoxicity. Human NK cells may thus contribute to a cellular rejection of pig neuronal xenografts by ADCC, or following IL-2 activation, by a direct cytotoxic effect.


Effects of ketamine-xylazine and isoflurane on insulin sensitivity in dehydroepiandrosterone sulfate-treated minipigs (Sus scrofa domestica).
Isoflurane and ketamine-xylazine (KX) combinations are widely used veterinary anesthetics, KX being the particularly common agent for immobilizing swine. Results of previous studies indicate that KX and xylazine suppress insulin release. The steroid hormones, dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS), have variable effects on insulin sensitivity in animals. We evaluated the effect of DHEAS on plasma glucose and insulin concentrations in female Yucatan swine under KX and isoflurane anesthesia. A 2 x 2 factorial design was used. Twenty-four 17-week-old gilts were randomly assigned to receive vehicle (placebo) or DHEAS as part of an ongoing study. The KX was given intramuscularly to all animals prior to blood sample collection at weeks two and four. At week three, all animals received isoflurane by inhalation. During KX anesthesia, mean insulin concentration in DHEAS-treated and control groups approximated half the postisoflurane values (P < 0.001). While under isoflurane, the DHEAS group had significantly higher mean plasma insulin concentration and mean insulin-to-glucose ratio, compared with values for controls (P < 0.05). These findings are consistent with changes in insulin values following DHEAS treatment observed previously in nonanesthetized swine. The effect of DHEAS treatment was absent in animals under KX anesthesia. These results suggest that KX significantly decreases plasma insulin concentration and blunts DHEAS-associated insulin resistance in female minipigs.


Nitroxide side-chain dynamics in a spin-labeled helix-forming peptide revealed by high-frequency (139.5-GHz) EPR spectroscopy.
High-frequency electron paramagnetic resonance (EPR) spectroscopy has been performed on a nitroxide spin-labeled peptide in fluid aqueous solution. The peptide, which follows the single letter sequence, was reacted with the methanethiosulfonate spin label at the cysteine sulfur. The spin sensitivity of high-frequency EPR is excellent with less than 20 pmol of sample required to obtain spectra with good signal-to-noise ratios. Simulation of the temperature-dependent spectral lineshapes reveals the existence of local anisotropic motion about the nitroxide N-O bond with a motional anisotropy tau( perpendicular)/tau( parallel) ( identical with N) approaching 2.6 at 306 K. Comparison with previous work on rigidly labeled peptides suggests that the spin label is reorienting about its side-chain tether. This study demonstrates the feasibility of performing 140-GHz EPR on biological samples in fluid aqueous solution.


Mesorectal fat area as a useful predictor of the difficulty of robotic-assisted laparoscopic total mesorectal excision for rectal cancer.
Various predictors of the difficulty of total mesorectal excision for rectal cancer have been described. Although a bulky mesorectum was considered to pose technical difficulties in total mesorectal excision, no studies have evaluated the influence of mesorectum morphology on the difficulty of total mesorectal excision. Mesorectal fat area at the level of the tip of the ischial spines on magnetic resonance imaging was described as a parameter characterizing mesorectum morphology. This study aimed to evaluate the influence of clinical and anatomical factors, including mesorectal fat area, on the difficulty of total mesorectal excision for rectal cancer. This study enrolled 98 patients who underwent robotic-assisted laparoscopic low anterior resection with total mesorectal excision for primary rectal cancer, performed by a single expert surgeon, between 2010 and 2015. Magnetic resonance imaging-based pelvimetry data were collected. Linear regression was performed to determine clinical and anatomical factors significantly associated with operative time of the pelvic phase, which was defined as the time interval from the start of rectal mobilization to the division of the rectum. The median operative time of the pelvic phase was 68 min (range 33-178 min). On univariate analysis, the following variables were significantly associated with longer operative time of the pelvic phase: male sex, larger tumor size, larger visceral fat area, larger mesorectal fat area, shorter pelvic outlet length, longer sacral length, shorter interspinous distance, larger pelvic inlet angle, and smaller angle between the lines connecting the coccyx to S3 and to the inferior middle aspect of the pubic symphysis. On multiple linear regression analysis, only larger mesorectal fat area remained significantly associated with longer operative time of the pelvic phase (p = 0.009). Mesorectal fat area may serve as a useful predictor of the difficulty of total mesorectal excision for rectal cancer.


Elevated serum Chlamydia trachomatis IgG antibodies. Association with decreased implantation rates in GIFT.
To analyze the impact of elevated Chlamydia IgG antibody (Ab) titers on the outcome of gamete intrafallopian transfer (GIFT) cycles. We retrospectively evaluated all the GIFT cycles in a five-year period performed at our center. One hundred one women under 40 years of age undergoing a total of 112 consecutive GIFT cycles were included. Twenty-six cycles (23.2%) were in women with elevated serum Chlamydia IgG Ab, and 86 (76.8%) were in women with negative titers. There were no significant differences in mean age, number of mature oocytes obtained or number of oocytes transferred between the two groups. Patients with elevated IgG Ab had clinical and ongoing pregnancy rates (PR) of 34.6% and 23.1%, respectively, and an implantation rate (IR) of 7.1% (13/184) as compared to a clinical and ongoing PR of 47.7% and 40.7%, respectively, and an IR of 16.5% (61/369) in the negative Ab group, respectively (P = NS for clinical and ongoing PR, P = .003 for IR). No ectopic pregnancies were noted in either group. The incidence of early pregnancy loss was 33.3% (3/9) and 14.6% (6/41) in the positive and negative Ab groups, respectively (P = .40). The presence of elevated serum Chlamydia IgG Ab was associated with a significantly lower implantation rate, a trend toward a lower PR and a trend toward a higher early pregnancy loss rate as compared to women with negative Ab titers. This group may represent a subset of assisted reproductive technology patients who are less likely to benefit from GIFT.


Motional heating in a graphene-coated ion trap.
Electric field noise originating from metal surfaces is a hindrance for a variety of microengineered systems, including for ions in microtraps, but is not well understood at the microscopic level. For trapped ions, it is manifested as motional-state decoherence inexplicable by thermal noise of electrodes alone, but likely surface-dependent. Here, we investigate the role of surface properties in motional heating by creating an ion trap with a unique exterior. Using single trapped-ion probes, we characterize copper electrodes covered in monolayer graphene, a material free of surface charge and dangling bonds. Surprisingly, we measure an average heating rate of 1020 ± 30 quanta/s, which is ∼100 times higher than typical for an uncoated trap operated under similar conditions. This may be related to hydrocarbon deposits on the surface, which could be monitored on graphene to potentially elucidate the mechanisms of motional heating on the atomic scale.


[Chemical constituents of Armillaria mellea mycelium. VI. Isolation and structure of armillaripin].
A new protoilludane sesquiterpenoid aromatic ester, named armillaripin, C24H30O6, mp 202-204 degrees C, [alpha]D15 + 130 degrees (c 0.055, CHCl3), was isolated from the petroleum ether extract of the artificially cultured mycelium of Armillaria mellea (Vahl. ex Fr.) Quel. (Tricolometaceae) by silica gel chromatography. On the basis of spectral (UV, IR, 1HNMR 13CNMR and MS) analysis its structure was deduced as I and confirmed by single-crystal X-ray analysis.


[Criteria for intensive treatment of hepatic coma].
Results observed over a period of two years in the intensive care of hepatic coma at the University of Genova surgical pathology department are briefly surveyed. A set of practical suggestions is offered for the management of patients whose prognosis is not open to change by the administration of conventional forms of treatment. A critical appraisal of the results achieved is presented along with the general series.


The conformation of glucagon: predictions and consequences.
It is proposed that glucagon, a polypeptide hormone, is delicately balanced between two major conformational states. Utilizing a new predictive model [Chou, P.Y., and Fasman, G.D. (1974), Biochemistry 13, 222] which considers all the conformational states in proteins (helix, beta sheet, random coil, and beta turns), the secondary structural regions of glucagon are computed herein. The conformational sensitivity of glucagon may be due to residues 19-27 which have both alpha-helical potential (mean value of Palpha = 1.19) as well as beta-sheet potential (mean value of Pbeta = 1.25). Two conformational states are predicted for glucagon. In predicted form (a), residues 5-10 form a beta-sheet region while residues 19-27 form an alpha-helical region (31% alpha, 21% beta) agreeing well with the circular dichroism (CD) spectra of glucagon. The similarity in the CD spectra of glucagon and insulin further suggests the presence of beta structure in glucagon, since X-ray analysis of insulin showed 24% beta sheet. In predicted form (b), both regions, residues 5-10 and residues 19-27, are beta sheets sheets (0% alpha, 52% beta) in agreement with the infrared spectral evidence that glucagon gels and fibrils have a predominant beta-sheet conformation. Since three reverse beta turns are predicted at residues 2-5, 10-13, and 15-18, glucagon may possess tertiary structure in agreement with viscosity and tritium-hydrogen exchange experiments. A proposal is offered concerning an induced alpha yields beta transition at residues 22-27 in glucagon during receptor site binding. Amino acid substitutions are proposed which should disrupt the beta sheets of glucagon with concomitant loss of biological activity. The experimental findings that glucagon aggregates to form dimers, trimers, and hexamers can be explained in terms of beta-sheet interactions as outlined in the present predictive model. Thus the conflicting conclusions of previous workers, concerning the conformation of glucagon in different environments, can be rationalized by the suggested conformational transition occurring within the molecule.


Supramolecular polymeric micelles by the host-guest interaction of star-like calix[4]arene and chlorin e6 for photodynamic therapy.
A supramolecular drug delivery system has been developed via the self-assembly of a supramolecular amphiphilic polymer, which is constructed by the host-guest interaction of hydrophilic PEGylated calix[4]arene and hydrophobic photosensitizer chlorin e6. It provides a new strategy for the preparation of supramolecular polymeric micelles, and plays an important role in biological applications.


Determination of surface area and porosity of small, nanometer-thick films by quartz crystal microbalance measurement of gas adsorption.
The Brunauer-Emmett-Teller (BET) surface area of 15 nm-thick films made of TiO2/polyelectrolyte bilayer was determined by quartz crystal microbalance (QCM) measurement of N2 and Ar adsorption isotherms at 77 K. The measurements were carried out using a home-built vacuum chamber that includes built-in 9 MHz QCM and cryostat units. As little as 1 ng of the adsorbed gas could be detected, and the BET surface area of a flat Au film (ca. 0.5 cm2) on an oscillator was determined within an experimental error of +/-5%. The titania/polymer composite film gives N2 and Ar adsorption isotherms consisting of a less-pronounced type-I curve and a break at around p/p0 = 0.7. This behavior is ascribed to the presence of irregular micropores and 6 nm phi-mesopores in the composite film. An analysis of the isotherms shows that the porosity of the composite film is about 12%, which is much smaller than that of bulk titania gel powder. The greater density appears to be related to the reported superior properties (robustness and resistance to electrical breakdown) of the organic/inorganic multilayer film. We conclude that the QCM-based, high-precision measurement of gas adsorption is a powerful tool for investigation of the detailed morphology of nanometer-thick films.


Omphalocele and gastroschisis and associated malformations.
The etiology of gastroschisis and omphalocele is unclear and their pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with omphalocele and gastroschisis, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 86 patients with omphalocele, 64 (74.4%) had associated malformations. These included patients with chromosomal abnormalities (25, 29.0%); non-chromosomal syndromes including Beckwith-Wiedemann syndrome, Goltz syndrome, Marshall-Smith syndrome, Meckel-Gruber syndrome, Oto-palato-digital type II syndrome, CHARGE syndrome, and fetal valproate syndrome; malformation sequences, including ectopia cordis, body stalk anomaly, exstrophy of bladder, exstrophy of cloaca, and OEIS (Omphalocele, Exstrophy of bladder, Imperforate anus, Spinal defect); malformation complexes including Pentalogy of Cantrell, and non-syndromic multiple congenital anomalies (MCA) (26, 30.2%). Malformations of the musculoskeletal system (31, 23.5%), urogenital system (27, 20.4%), cardiovascular system (20, 15.1%), and central nervous system (12, 9.1%) were the most common other congenital malformations in patients with omphalocele and non-syndromic MCA. Of the 60 patients with gastroschisis, 10 (16.6%) had associated malformations. In contrast to omphalocele, gastroschisis was rarely associated with a complex pattern of malformation, that is, one each (1.7%) with a chromosomal abnormality (trisomy 21), sequence (amyoplasia congenita), unspecified dwarfism, and 7 (11.7%) with MCA. We observed a striking difference in the prevalence of total malformations (74.4% vs. 16.6%, P < 0.001) and specific patterns of malformations associated with omphalocele and gastroschisis which emphasizes the need to evaluate all patients with omphalocele and gastroschisis for possible associated malformations. Malformation surveillance programs should be aware that the malformations associated with omphalocele can be often classified into a recognizable malformation syndrome or pattern (44.2%).


Self-assembly of strongly dipolar molecules on metal surfaces.
The role of dipole-dipole interactions in the self-assembly of dipolar organic molecules on surfaces is investigated. As a model system, strongly dipolar model molecules, p-benzoquinonemonoimine zwitterions (ZI) of type C6H2(⋯ NHR)2(⋯ O)2 on crystalline coinage metal surfaces were investigated with scanning tunneling microscopy and first principles calculations. Depending on the substrate, the molecules assemble into small clusters, nano gratings, and stripes, as well as in two-dimensional islands. The alignment of the molecular dipoles in those assemblies only rarely assumes the lowest electrostatic energy configuration. Based on calculations of the electrostatic energy for various experimentally observed molecular arrangements and under consideration of computed dipole moments of adsorbed molecules, the electrostatic energy minimization is ruled out as the driving force in the self-assembly. The structures observed are mainly the result of a competition between chemical interactions and substrate effects. The substrate's role in the self-assembly is to (i) reduce and realign the molecular dipole through charge donation and back donation involving both the molecular HOMO and LUMO, (ii) dictate the epitaxial orientation of the adsorbates, specifically so on Cu(111), and (iii) inhibit attractive forces between neighboring chains in the system ZI/Cu(111), which results in regularly spaced molecular gratings.


Characteristics and treatment outcome of patients requiring additional intravenous analgesia during extracorporeal shockwave lithotripsy with Dornier Compact Delta Lithotriptor.
To investigate the effect of additional intravenous analgesia (besides oral analgesic premedication) on the treatment outcome in patients receiving extracorporeal shock wave lithotripsy (SWL) with Dornier Compact- Delta lithotriptor. Five hundred and twenty adults receiving SWL for solitary urinary stone of size </=10 mm were retrospectively reviewed. They received the same analgesic protocol--oral diclofenac 50 mg as premedication and additional intravenous bolus alfentanil if they experienced discomfort during ESWL. After reviewing the analgesic usage, they were divided into two groups, Group-A--received oral analgesic alone and Group-B--received both oral and additional intravenous analgesia during ESWL. Treatment outcome of the two groups was then compared. There were 306 patients in Group-A and 214 patients in Group-B. The stone-free rates at 3-month for Group-A and -B were 38.2% and 44.9% respectively (P = 0.100). The re-treatment/auxiliary procedure rates for the Group-A and Group-B were 40.8%/12.7%, and 35.0%/18.2% respectively. The additional use of intravenous analgesia improved the effectiveness quotient by 17.7% [from 0.249 (Group-A) to 0.293(Group-B)]. The additional use of intravenous analgesia during SWL with Dornier Compact Delta lithotriptor resulted in improvement of effectiveness quotient.


Transformations of glycolysis control characteristics in human erythrocytes during blood storage.
Changes in glycolysis control characteristics (dependence of glycolysis rate on ATP concentration) in erythrocytes were studied during the storage of donors blood with glucose citrate hemoconservant. During the first two weeks of storage the shape of glycolysis control characteristics in the erythrocytes could be shown to remain practically unchanged, which was represented by a bell-shaped curve such as in fresh erythrocytes. During this period the physiological point of glycolysis will move along the glycolysis control characteristics towards the maximum of the curve. Once the maximum of the physiological point has been reached, the shape of the curve can be seen to change. The maximum on the curve becomes less evident, moving down and to the left from its initial position. These changes will occur after two to four weeks of storage. In some cases the maximum on glycolysis control characteristics will disappear at the latest stages of storage. The changes observed will occur in blood of different donors at different moments of storage. The nature of the changes observed and their influence on erythrocyte viability are discussed.


Bioavailability of a new sustained-release theophylline capsule in fasted and non-fasted healthy subjects: single and multiple dosing studies.
Eighteen healthy, non-smoking, adult volunteers participated in single and multiple dose three-way crossover studies to evaluate a sustained-release, pellet-filled capsule of theophylline, Austyn. The effect of food on the bioavailability of the sustained-release capsule was investigated by administering 300 mg single doses of Austyn, with a high-fat meal and without food and a divided 300 mg dose of the reference product Elixophyllin elixir, given after fasting. Plasma theophylline concentrations were measured by fluorescence polarization immunoassay (FPIA) which had been validated against HPLC. The single dose study data showed that there were no significant differences (n = 18, ANOVA, p greater than 0.05) between the three regimens with respect to AUC0-infinity values (mg h l-1), (mean +/- SD); Elixophyllin fasting = 97.1 +/- 33.7, Austyn with food = 90.9 +/- 31.3, Austyn fasting = 91.2 +/- 33.8. Similarly, multiple dosing with rapid-release Nuelin tablets, Austyn capsules, and sustained-release Theo-Dur tablets demonstrated that there were no significant differences between regimens with respect to AUC0-24h, AUC0-12h, and AUC12-24h values calculated from the steady-state concentrations (5th day, 24 h sampling). However, the percentage fluctuation at steady-state over the total blood sampling period was significantly less for treatment with the sustained-release capsule. Austyn, compared with the sustained-release tablet, Theo-Dur (Austyn = 36.7 +/- 13.7 per cent, Theo-Dur = 53.1 +/- 14.1 per cent). The results of the single and multiple dose studies indicate that Austyn capsules demonstrate complete bioavailability, and good controlled release characteristics not influenced by concomitant intake of a high-fat meal and with no evidence of dose dumping.