Room-temperature stabilization of nanoscale superionic Ag2Se.

Superionic materials are multi-component solids in which one sub-lattice exhibits high ionic conductivity within a fixed crystalline structure. This is typically associated with a structural phase transition occurring significantly above room temperature. Here, through combined temperature-resolved x-ray diffraction and differential scanning calorimetry, we map out the nanoscale size-dependence of the Ag2Se tetragonal to superionic phase transition temperature and determine the threshold size for room-temperature stabilization of superionic Ag2Se. For the first time, clear experimental evidence for such stabilization of the highly ionic conducting phase at room temperature is obtained in ∼2 nm diameter spheres, which corresponds to a >100 °C suppression of the bulk phase transition temperature. This may enable technological applications of Ag2Se in devices where high ionic conductivity at room temperature is required.

[DDB2-associated incidence of squamous cell carcinoma in Haflingers: risk minimization by genotyping]. / DDB2-assoziiertes Vorkommen von Plattenepithelkarzinomen beim Haflinger: Risikominimierung durch Genotypisierung.

INTRODUCTION: SCC (squamous cell carinomas) are among the most common eye neoplasms in horses. In recent studies Haflinger horses with a homozygous genotype for a missense variant in the DDB2 gene (damage specific DNA binding protein 2) had a significant increased risk of developing ocular SCC. The aims of this study were to determine the frequency of the SCC-associated risk allele in the DDB2 gene in Swiss and Austrian Haflinger populations and to validate the previously described phenotypic correlation. For this purpose, Haflingers presented at various horse clinics in Switzerland (n = 21, including 11 SCC cases), privately kept Haflingers (n = 52, including 1 SCC case), and Haflingers from a stud farm in the Austrian Tyrol (n = 53) were recruited. The individual DDB2 genotype of the animals was determined using a polymerase chain ceaction (PCR) test using hair follicle or whole blood samples. Of the 12 horses suffering from SCC, nine had ocular SCC and three had non-ocular SCC. Six of the nine Haflingers with ocular SCC and one of the three Haflingers with non-ocular SCC were homozygous for the DDB2 variant. Of the 113 clinically normal animals, 7/113 were homozygous (6 %) and 42/113 were heterozygous (37 %), which corresponds to an allele frequency of 24,8 % in the control cohort. The risk of ocular SCC occurring in Haflingers is significantly increased with the homozygous DDB2 genotype. However, not all animals with SCC carry this gene variant and not all DDB2 homozygous animals develop SCC, which can be explained by the multifactorial genesis of the disease. Due to the high frequency of the undesirable allele, we recommend taking the individual DDB2 genotype of breeding animals into account in order to avoid homozygous offspring with a greatly increased SCC risk by excluding high-risk matings.

INTRODUCTION: Les carcinomes épidermoïdes (CE) sont parmi les néoplasmes oculaires les plus fréquents chez les chevaux. Des études récentes ont montré que les chevaux Haflinger présentant un génotype homozygote pour un variant faux-sens dans le gène DDB2 (damage specific DNA binding protein 2) avaient un risque significativement plus élevé de développer un CE oculaire. Les objectifs de cette étude étaient de déterminer la fréquence de l'allèle à risque associé au CE dans le gène DDB2 dans les populations suisses et autrichiennes de Haflinger et de valider la corrélation phénotypique décrite précédemment. Pour ce faire, des Haflingers présentés dans différentes cliniques équines en Suisse (n = 21, dont 11 cas de CE), des Haflingers privés (n = 52, dont 1 cas de CE) et des Haflingers d'un haras du Tyrol autrichien (n = 53) ont été recrutés. Le génotype DDB2 individuel des animaux a été déterminé à l'aide d'un test de réaction en chaîne par polymérase (PCR) utilisant des échantillons de follicules pileux ou de sang total. Sur les 12 chevaux souffrant de CE, neuf avaient un CE oculaire et trois un CE non oculaire. Six des neuf Haflingers atteints de CE oculaire et un des trois Haflingers atteints de CE non oculaire étaient homozygotes pour la variante DDB2. Sur les 113 animaux cliniquement normaux, 7/113 étaient homozygotes (6 %) et 42/113 étaient hétérozygotes (37 %), ce qui correspond à une fréquence d'allèle de 24,8 % dans la cohorte de contrôle. Le risque de CE oculaire chez les Haflingers augmente de manière significative avec le génotype DDB2 homozygote. Cependant, tous les animaux atteints de CE ne sont pas porteurs de cette variante génétique et tous les animaux homozygotes DDB2 ne développent pas de CE, ce qui peut s'expliquer par la genèse multifactorielle de la maladie. En raison de la fréquence élevée de l'allèle indésirable, nous recommandons de tenir compte du génotype DDB2 individuel des animaux reproducteurs afin d'éviter une progéniture homozygote présentant un risque fortement accru de CE en excluant les accouplements à haut risque.

Hemoglobin Kinetics of the Galapagos Rift Vent Tube Worm Riftia pachyptila Jones (Pogonophora; Vestimentifera).

Kinetics of the reactions of Riftia pachyptila hemoglobin with oxygen were followed spectrophotometrically by stopped-flow and laser flash photolysis techniques. The rate of oxygen dissociation increases eightfold over the range of 5 degrees to 20 degrees C (k = 2.2 sec(-1)at 10 degrees C). Oxygen recombination after flash photolysis was biphasic. The rates of both slow and fast phases of the reaction were independent of temperature from 0 degrees to 20 degrees C(k'fast = 7 x 10(6); k'slow = 1 x 16(6) liter mole (-1) sec(-1)). As the oxygen affinity is relatively temperature independent, analysis in terms of the two-state model of cooperativity requires that the conformational equilibrium constant L decrease by about 50-fold between 3 degrees and 15 degrees C.

[Relationship between volume and quality of care for surgical interventions; results of a literature review]. / Verband tussen volume en kwaliteit van zorg bij heelkundige ingrepen; resultaten van een literatuuronderzoek.

OBJECTIVE: To examine the relationship between the number of procedures performed per hospital or per surgeon and health care outcomes. DESIGN: Literature review. METHOD: Relevant literature was identified using recent systematic reviews from Germany, England, France and the United States. The Cochrane Library, Medline and Embase were also searched for recent studies (2000-2005) published in German, English, French, or Dutch using the combined search terms 'surgery' and 'volume'; included studies reported mortality or morbidity as measures of health care quality. RESULTS: 5 systematic reviews were found, which described the results of a total of 41 relevant articles. 8 original articles of sufficient quality published since 2000 were also identified. Most of these articles were also included in the reviews. Relationships between volume per hospital and per surgeon and case fatality (or survival) and morbidity were found for a number of surgical procedures. The strongest associations between volume and case fatality were found for pancreatic and oesophageal resection and, to a lesser degree, elective repair ofabdominal aortic aneurysm. For other procedures the relationship was relatively weak, absent, or not studied. CONCLUSION: Volume appears to be related to quality for some surgical procedures. The magnitude of the relationship differs depending on the procedure. For technically less complex procedures, organisation within the hospital appears to have a greater influence on the differences between hospitals than the performing surgeon.

Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-(4-(5-Nitro-2-furyl)-2-thiazolyl)formamide.

The effect of vitamin A deficiency and hypervitaminosis A on the urothelial carcinogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formanmide (FANFT) was determined in female weanling Sprague-Dawley rats. Vitamin A deficiency resulted in squamous metaplasia of the urinary bladder and high incidences of cystitis, ureteritis, and pyelonephritis. Administration of FANFT to vitamin A-deficient rats appeared to accelerate the carcinogenic process, with earlier appearance of urinary bladder tumors and the development of ureteral and renal pelvic carcinomas. Most of these tumors were squamous cell, occasionally with transitional cell foci. Hypervitaminosis A prevented the appearance of squamous metaplasia and squamous cell neoplasia in rats fed FANFT, but it did not inhibit the formation of transitional cell hyperplasia or neoplasia in comparison to rats receiving normal levels of vitamin A and FANFT.

Nurses' health, age and the wish to leave the profession--findings from the European NEXT-Study.

BACKGROUND AND OBJECTIVES: In many industrialised countries the number of workers with low health is expected to increase in the nursing profession. This will have implications for occupational health work in health care. The European NEXT-Study (www. next-study. net, funded by EU) investigates working conditions of nurses in ten European countries and provides the opportunity to evaluate the role of health with respect to age and the consideration of leaving nursing. METHODS: 26,263 female registered nurses from Belgium, Germany, Finland, France, England, Italy, Netherlands, Poland and Slovakia were eligible for analysis. RESULTS: In most countries, older nurses considered leaving the profession more frequently than younger nurses. 'Health' was--next to 'professional opportunities' and 'work organisational factors'--strongly associated with the consideration of leaving nursing. However, more than half of all nurses with low health wanted to remain in the profession. This group reported rather positive psychosocial working conditions--but also the highest fear for unemployment. CONCLUSIONS: The findings indicate that 'the nurse with low health' is reality in many health care settings. Both positive supporting working conditions but also lack of occupational alternatives and fear of unemployment may contribute to this. Current economic, political and demographic trends implicate that the number of active nurses with low health will increase. Occupational health surveillance will be challenged by this. But NEXT findings implicate that prevention also will have to regard work organisational factors if the aim is to sustain nurses' health and to enable nurses to remain healthy in their profession until retirement age.

Structural bases for sulfide recognition in Lucina pectinata hemoglobin I.

The X-ray crystal structure of the sulfide derivative of ferric Lucina pectinata hemoglobin component I (HbI) has been determined at 1.9 A resolution (R-factor 0.186). The heme pocket structural organization of HbI is in keeping with its ligand binding properties. The fast sulfide association rate constant can be related to the presence of Gln(64)E7, as the heme distal residue, together with the protein structural properties in the CD-E distal region. Moreover, the very high sulfide affinity for HbI is reflected by the exceptionally slow ligand dissociation rate. The stabilization of the heme-bound sulfide molecule is achieved through hydrogen bonding to Gln(64)E7, as well as by finely tuned aromatic-electrostatic interactions with the clustered residues Phe(29)B10, Phe(43)CD1 and Phe(68)E11. Such a peculiar arrangement of phenylalanyl residues at the distal ligand binding site has not been observed before in the globin family, and is unique to HbI, a protein functionally devoted to sulfide transport.

Structure of the sulfide-reactive hemoglobin from the clam Lucina pectinata. Crystallographic analysis at 1.5 A resolution.

The crystal structure of the aquo-met form of the sulfide-reactive hemoglobin (component I) from the gill of the symbiont-harboring mollusc, Lucina pectinata, has been solved and refined at 1.5 A resolution, based on synchrotron radiation X-ray diffraction data, and employing molecular replacement techniques. The crystallographic R-factor, calculated for the data in the 15.0 to 1.5 A resolution range, is 0.170, with highly regular stereochemical parameters for the protein model, and including 131 water molecules. The monomeric hemoglobin I chain consists of 142 amino acid residues, which have been partly identified on the basis of the crystallographic analysis. The molecule is characterized by an unusual distribution of aromatic residues, particularly in the region surrounding the distal site in the heme pocket. The heme distal residue is Gln(64)E7, while other notable amino acid substitutions include Trp(21)B2, Phe(29)B10, Leu(46)CD3, Phe(68)E11 and Trp(75)E18. An amino acid insertion (Ser44) is observed between sites CD1 and CD2. In the aquo-met protein, a water molecule is present at the sixth coordination position of the heme iron, and hydrogen bonded to Gln(64)E7. Simple model building shows that a dioxygen molecule, bound to ferrous protein, would contact with its free atom the ring edge of Phe(29)B10, being thus stabilized at the coordination site by an aromatic-electrostatic interaction. Similarly, the unique packing and organization of aromatic residues in the surroundings of the heme distal site is proposed as the molecular basis of the very high affinity of Lucina pectinata hemoglobin I for hydrogen sulfide, considered as one of the two physiological ligands of the protein.

Crystallization and preliminary data for the ferric form of Lucina pectinata hemoglobin I.

Cytoplasmic monomeric hemoglobin I from the bacteria-harboring gill of the bivalve mollusc Lucina pectinata has been crystallized in a form suitable for atomic resolution X-ray structural investigations. The crystals have been grown at pH 4.8, in 0.05 M-acetate buffer, using 2.6 M-ammonium sulfate as precipitating agent. The crystals belong to the monoclinic space group P2(1), with unit cell constants a = 50.0 A, b = 38.6 A, c = 42.1 A, beta = 107.1 degrees, and contain one molecule (14,000 Mr) in the asymmetric unit. By means of single crystal microspectrophotometry it has been shown that the crystals contain the ferric form of L. pectinata "sulfide reactive" hemoglobin I. On the other hand, by careful control of the buffering medium composition, it has been possible to obtain stable crystals of the deoxy, oxy and sulfide forms of the protein.

Crystallization of a complex of hemoglobin components II and III of the symbiont-harboring clam Lucina pectinata.

Diffraction data to 3.1 A resolution were collected on crystals of a complex of components II and III of the cytoplasmic hemoglobin of the symbiont-harboring clam Lucina pectinata. The crystal system is tetragonal, a = 76.3 A, c = 153.1 A and the space group is P42212. The asymmetric unit probably contains a dimer of the tetrameric complex.

Nonsteric factors dominate binding of nitric oxide, azide, imidazole, cyanide, and fluoride to the rhizobial heme-based oxygen sensor FixL.

BACKGROUND: The FixL protein is a heme-based sensor. Binding of oxygen to a unique heme domain inhibits a kinase domain of the type found in two-component regulators. Oxygen association is slow, but the dissociation rate is comparable to that of myoglobins. We have probed the size and chemistry of the FixL heme pocket by measuring the affinites, on rates and off rates for a wide variety of ferric heme ligands. Cyanide, but not fluoride, regulates the kinase activity. To examine how the sensory heme domain interacts with the kinase, we asked how the presence of the kinase domain affects ligand binding. RESULTS: The affinities of ferric FixL for heme ligands follow the same trend as their pKa values: cyanide > 4-methyl imidazole > imidazole > fluoride > azide >> thiocyanate. The association rates follow the reverse trend. Striking differences from myoglobin include a 6-fold greater affinity for, and faster binding to, the bulky ligand imidazole, a 14-fold faster on rate for nitric oxide, a 2 800-fold lower affinity for azide, and a complete failure to bind thiocyanate. The presence of the kinase domain does not alter the affinity or binding kinetics of the high-spin ligand fluoride, but affects the off rates of other ligands. The EPR spectrum shows a characteristic pentacoordinate nitrosyl heme, indicating that the Fe-His bond in FixL is strained. CONCLUSIONS: The importance of ligand deprotonation to the on rates and the fact that large ligands bind readily indicate that the heme pocket is open and apolar. Ligand basicity strongly influences the strength of binding. The destabilization of inhibitory ligands by the presence of the kinase domain is consistent with a 'load' imposed by coupling to the inactivating mechanism.

Circular dichroism spectroscopy of Lucina I hemoglobin.

The monomeric hemoglobin from the mollusc Lucina pectinata (HbI) represents an interesting model system for the study of heme-related circular dichroic (CD) bands in view of the highly asymmetric distribution of aromatic residues around the heme pocket revealed by the X-ray crystal structure. The CD spectra of both ferrous and ferric HbI derivatives exhibit negative CD bands in the Soret and ultraviolet region with an enhanced ellipticity of the heme N and L bands in the near-UV region. In contrast, the magnitude of the Cotton effect in the visible and Soret regions is comparable to that observed in other hemoproteins. The spectrum of the carbon monoxide derivative shows a surprising similarity with that observed for the soybean leghemoglobin carbon monoxide adduct. A common structural feature in the two proteins is the presence in the distal pocket of two Phe residues (B9 and B10) the aromatic rings of which are perpendicular to the heme plane.

Assessment of drug intervention on the ischemic myocardium: serial imaging and measurement with computerized tomography.

Computerized tomography was evaluated as a technique for imaging and measuring the effect of an intervention on acutely ischemic myocardium. Because cell edema occurs with acute myocardial ischemia and decreases the X-ray attenuation coefficients (tissue density) of myocardium, computerized tomographic images were used to quantitate the effect of hyperosmotic mannitol on ischemia-induced edema. Canine hearts were arrested and scanned after (1) temporary occlusion of the proximal circumflex artery followed by reflow of blood, or (2) continued occlusion of the distal left anterior descending coronary artery. X-ray attenuation values (Hounsfield units) were linearly related to tissue wet/dry weight ratios (r = 0.87, P less than 0.001). After 2 hours of occlusion of the left anterior descending coronary artery the hearts that received mannitol manifested a significant reduction (P less than 0.05) in the volume of left ventricular wall involved with edema. Although the area of edema measured with computerized tomography tended to be smaller in the hearts treated with mannitol than in untreated hearts subjected to a 6 hour occlusion of the left anterior descending coronary artery, the size of the lesion was variable and did not differ significantly from that in untreated hearts. With either short periods of circumflex arterial occlusion followed by blood reflow or with 2 or 6 hours of prolonged occlusion of the left anterior descending coronary artery, the difference in mean attenuation coefficients between the ischemic and nonischemic areas of myocardium in mannitol-treated and untreated hearts was significantly less. These results indicate that computerized tomography in the arrested heart can detect and quantitate the lesion of early acute myocardial ischemia and can quantitate the effect of drug intervention.

Definition of cardiac structures using computerized tomography in isolated arrested and beating canine hearts.

Computerized axial tomography of the brain is a revolutionary noninvasive technique that has provided remarkable resolution of intracerebral structures. This study was undertaken to determine the potential of computerized tomography for defining the anatomy of 40 arrested and 9 beating (ejecting left heart preparation) canine hearts. Using an EMI cranial unit, scanning was performed in hearts under in vitro conditions with a lactated Ringer's interface. The tomographic scans obtained were later compared with comparable 8 mm thick sections of the heart. At physiologic levels of hematocrit (range 36 to 45%) external structures were well defined, but because of the lack of a differential between cavitary and myocardial densities, it was not possible to distinguish intracardiac structures. With very small amounts of iodinated contrast material (remotely administered in the case of the beating hearts) or with anemia (hematocrit less than 33%), the right and left ventricular cavities became clearly visible in both horizontal and longitudinal tomographic scans. It was possible to distinguish readily the boundaries of the ventricular and atrial cavities, the papillary muscles, the major trabeculae and the aorta. Rhythmic motion of the beating heart, suspended in its pericardium, did not eliminate structural definition. Thus, computerized tomography provides a new approach to the definition of cardiac structure with a relatively high degree of resolution. These observations point to the potential usefulness of this noninvasive technique for the evluation of both cardiac function and ventricular wall abnormalities.

ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented.

Computerized tomography of ischemic myocardium: quantitation of extent and severity of edema in an in vitro canine model.

The capacity of computerized tomography to assess myocardial edema resulting from acute coronary occlusion was investigated in 19 arrested and 2 beating canine hearts. Edematous myocardium was consistently detected as areas of decreased attenuation values. The magnitude of the decrease in attenuation value was linearly related to the severity of the edema. The anatomic definition and tomographic information in the arrested hearts provided the capability for localization and quantitation of the extent of the lesion. The results of these in vitro investigations indicate that CT scanning is a technique which will contribute important pathophysiologic information about the evolution of myocardial ischemia.

AUR Memorial Award 1993. A drug system (PDH) for interventional radiology. Synthesis, properties, and efficacy.

RATIONALE AND OBJECTIVES: The authors synthesized and tested a novel hydrogel system proposed for use in extra- and intravascular radiologic interventions, such as chemoembolizations and embolizations, and as a vehicle for sustained drug release. MATERIALS: The material was specifically designed to meet the prerequisites of biodegradation, biocompatibility, low immunogenicity, low toxicity, and easy use. The material consists of a protein backbone cross-linked with activated bifunctional polyethyleneglycol (PEG) derivatives (PEG-derivatized hydrogel, [PDH]) to which are attached therapeutic (e.g., doxorubicin, a chemotherapeutic agent = PDH-dx) or diagnostic labels (e.g. Gd-DTPA). RESULTS: PDH-dx effectively reduced the risk of local tumor recurrence in a rat model when implanted locally after surgical tumor removal. After administration, PDH is degraded by proteases release from macrophages; implantations of 1 mL samples into paraspinal muscles of rats were completely absorbed within 4 weeks and its constituents were metabolized. Antibody titers (total Ig response) against the PDH were not detectable 1 week after implantation, whereas protein control substances elicited a strong response. CONCLUSIONS: PDH and its derivatives are relatively nontoxic, biodegradable materials for use in radiologic interventions and as a vehicle for sustained drug release.

Intravenous cholangiography in the rhesus monkey. part I: Determination of optimal iodipamide dose during a one-hour infusion.

One-hour infusion intravenous cholangiography with iodipamide was performed in 3 rhesus monkeys with intact enterohepatic circulations. A series of four different doses including standard (0.3 ml/kg) and "double dose" (0.6 ml/kg) levels were compared. The 0.6 ml/kg dose resulted in significantly higher biliary iodine excretion and concentration than the lower two doses. A 1.2 ml/kg dose probably increased biliary iodine concentration a small amount when compared to the 0.6 ml/kg dose but did not increase iodine excretion. Peak iodine excretion and concentration occurred, on the average, at one hour. The excretion of iodine in the bile demonstrated no inhibitory effect on the concomitant excretion of bile salts.

Preoperative staging and assessment of resectability of pancreatic cancer.

To study the accuracy of preoperative staging techniques for assessing resectability of pancreatic and ampullary adenocarcinoma, we entered 88 consecutive candidates into a prospective study of contrast-enhanced computed tomography, magnetic resonance imaging, angiography, and laparoscopy. Resectability was proved in 16 (29%) of 55 patients for the head of the pancreas, 1 (6%) of 17 for the body and tail of the pancreas, and 14 (88%) of 16 for the ampulla. The combined findings of computed tomography and angiography showed that more than 87% of pancreatic head tumors were unresectable because of vascular encasement, but neither modality sufficed alone. Small liver and peritoneal metastases were found in 15 (27%) of 55 cancers of the head of the pancreas, 11 (65%) of 17 cancers of the body and tail of the pancreas, and 1 (6%) of 16 cancers of the ampulla; computed tomography missed all but 2 of these instances of metastasis, but laparoscopy with biopsy identified 22 (96%) of 23 instances. Magnetic resonance imaging findings did not differ significantly from computed tomography and conferred no added benefit. Ninety percent of unresectable tumors were identified. Seventy-eight percent of pancreatic head cancers were resectable when all test results were negative vs 5% (2/37) when any test result was positive. This study demonstrates that accurate and efficient triage is possible for patients with cancer of the pancreas and ampulla.

Percutaneous drainage of diverticular abscess. An adjunct to surgical therapy.

We undertook this study to determine whether a computed tomography-guided, percutaneous preoperative drainage of a peridiverticular abscess can safely allow a one-stage procedure in patients requiring surgery for acute diverticulitis. In 17 patients evaluated prospectively by computed tomography, thin-needle aspiration demonstrated purulent fluid collection in 11 patients. Percutaneous catheter drainage was undertaken in eight patients. In the three remaining patients, the abscess was either too small to warrant drainage or no safe access route was present. Seven of eight patients had a single-stage resection within one to three weeks of percutaneous catheter drainage. There were no complications. Our studies suggest that a combined radiological-surgical approach has the potential to reduce morbidity and hospital costs without increasing mortality in the management of perforated colon diverticulitis with associated abscess formation.