bluuebunny/crossref_metadata_2025 huggingface dataset:
Sudden death in young athletes.
Authors: Maron B J , Roberts W C , McAllister H A , Rosing D R , Epstein S E
Published: June 2012

The causes of sudden and unexpected death in 29 highly conditioned, competitive athletes, ages 13-30 years, are summarized. Sudden death occurred during or just after severe exertion on the athletic field in 22 of the 29 athletes. Structural cardiovascular abnormalities were identified at necropsy in 28 of the 29 athletes (97%), and in 22 (76%) were almost certainly the cause of death. The most common cause of death in this series was hypertrophic cardiomyopathy, which was present in 14 athletes. Other cardiovascular abnormalities that occurred in more than one athlete were anomalous origin of the left coronary artery from the right (anterior) sinus of Valsalva, idiopathic concentric left ventricular hypertrophy, coronary heart disease and ruptured aorta. Cardiac disease was suspected during life in only seven of the 29 patients, and in only two of the seven was the correct diagnosis made clinically. Hence, in this series of young athletes, sudden death was usually due to structural cardiovascular disease, and hypertrophic cardiomyopathy was a frequent cause of sudden death; atherosclerotic coronary heart disease was relatively uncommon.
Porcine xenograft valves. Long-term (60-89-month) follow-up.
Authors: Lakier J B , Khaja F , Magilligan D J , Goldstein S
Published: June 2012

An analysis of 211 patients who had porcine xenograft valve replacements at Henry Ford Hospital between October 1971 and March 1974, was accomplished, with 100% follow-up. The follow-up period extended from 60-89 months after implantation. One hundred sixty-seven patients with 192 valves survived the perioperative period and were subjected to life table analysis. Hemodynamically significant porcine xenograft degeneration that required reoperation occurred in 18 patients, two of whom had infective endocarditis. Only four valves failed within 48 months of surgery. Ten of 42 (23.8%) patients with isolated aortic valve replacement and eight of 102 patients (7.8%) patients with isolated mitral valve replacement required reoperation (p < 0.01). In patients under 25 years of age, six of nine surviving patients had repeat operations. Our data indicate that porcine xenograft degeneration is related to the duration of implantation and the age of the patient at the time implantation was performed. In addition, porcine xenograft valves in the aortic position are more likely to degenerate than are those in the mitral position.
Ventricular tachycardia in infancy: evidence for a reentrant mechanism.
Authors: Gaum W E , Schwartz D C , Kaplan S
Published: June 2012

Ventricular tachycardia is unusual in infancy. Three infants are described in whom this arrhythmia was documented by electrophysiologic studies. The ability to start and terminate this rhythm by critically timed premature ventricular stimulation suggests a reentrant mechanism. All three patients have remained free of arrhythmias on oral propranolol therapy.
Qualitative real-time cross-sectional echocardiographic imaging of the human fetus during the second half of pregnancy.
Authors: Lange L W , Sahn D J , Allen H D , Goldberg S J , Anderson C , Giles H
Published: June 2012

In this study, we used high-resolution echocardiographic systems to investigate how early in pregnancy normal fetal cardiac anatomy could be noninvasively evaluated. Over a 2-year period, 84 of 88 fetuses were successfully imaged (27 were studied serially). Postnatal images of 73 were obtained during the newborn period. Estimated fetal age varied at initial examination from 19-41 weeks (mean +/- 0.5 weeks [+/- SEM]) of pregnancy. Estimated fetal weight using an ultrasound algorithm varied from 500-3100 g (mean 1580 +/- 80 g [+/- SEM]). To evaluate fetal cardiac anatomy, we reproduced commonly used cross-sectional views of the heart. The four-chamber and the short-axis great artery views have been most successful for cardiac evaluation in the fetus. These views could be obtained in 96% and 95% of the patients, respectively. With these views, cardiac chamber and valve structures, as well as two great arteries, could be imaged in detail. The ascending and descending aorta, as well as the aortic arch and vessels to the arms and head, were visualized in 87% of examinations, and the inferior and superior venae cavae were visualized in 76%. In two of three RH fetuses, changes in cardiac chambers compatible with hydrops fetalis were demonstrated. We examined all fetuses after birth and verified clinically (or noninvasively) that no cardiac malformations were present. It appears, however, that the diagnosis of major congenital heart defects should be possible before birth.
The relevance of platelet and fibrin thromboembolism of the coronary microcirculation, with special reference to sudden cardiac death.
Authors: El-Maraghi N , Genton E
Published: June 2012

The coronary microcirculation was examined for platelet and fibrin thrombi in hearts from 21 normal subjects and 244 cardiac patients, including 168 with ischemic heart disease (IHD) and 76 with other types of heart disease. Seventy-seven cases were sudden cardiac death (SCD). No microthrombi were present in any of the normal hearts, whereas platelet and fibrin thrombin were present in the coronary microcirculation in 32 of 244 cardiac cases (13.1%), including 19 with IHD and 13 with other types of heart disease and after cardiac surgery. The microthrombi were either embolic or represented in situ thrombosis, depending upon the underlying pathologic process. There was no significant difference in the incidence of microthrombi in SCD patients, with IHD (10 of 50, 20%) compared with patients who survived longer (nine of 93, 10%). In SCD patients, however, platelet microthrombin were more frequent in patients less than 45 years of age compared with those older than 45 years of age (p = 0.0002). We concluded that coronary microcirculatory thrombi are not uncommon in heart disease. A subgroup of SCD in young patients with IHD has been identified in whom microcirculatory platelet thrombosis is the main cardiac pathologic process. The significance of this process is emphasized by the associated myocardial damage.
Effect of Dibenzyline on Skin Temperature, Peripheral Blood Flow, and Vasomotor Responses in Normal Patients and Patients with Increased Vasoconstrictor Tone
Authors: MOSER MARVIN , WATKINS DALE , MORRIS NEAL , PRANDONI ANDREW G. , MATTINGLY THOMAS W.
Published: June 2012

Dibenzyline is an orally effective, moderately potent, long acting, adrenergic blocking agent. The drug is capable of at least partially preventing the vasoconstrictor responses to cold and to injected Neosynephrine. Blood flow and temperature responses to this agent do not always parallel results obtained following surgical sympathectomy, but the degree of effect appears to be sufficient to produce a clinical response. Side effects and the development of "tolerance" may limit the use of Dibenzyline in clinical medicine.
Tetralogy of Fallot with Unilateral Pulmonary Atresia
Authors: NADAS ALEXANDER S. , ROSENBAUM HAROLD D. , WITTENBORG MARTIN H. , RUDOLPH ABRAHAM M.
Published: June 2012

Four patients with tetralogy of Fallot syndrome, whose physical and x-ray findings were distinctly unusual, are presented in this report. All these patients were demonstrated to have functional or anatomic atresia of one of the main pulmonary arteries, in addition to the characteristic features of the tetralogy of Fallot. Diagnostic criteria, including angiocardiograms, are presented, and the therapeutic implications are discussed.
The Electrocardiographic Pattern of Hypopotassemia with and without Hypocalcemia
Authors: SURAWICZ BORYS , LEPESCHKIN EUGENE
Published: June 2012

Detailed analysis of the electrocardiogram in patients with hypopotassemia without hypocalcemia showed that the Q-U interval and its components (Q-oT, Q-aT, Q-T, and Q-aU) have essentially the same duration as in normal subjects for the same heart rate and sex. The typical hypopotassemia pattern is characterized by progressive depression of S-T, lowering and inversion of T and increase of U in left precordial leads. In hypopotassemia with hypocalcemia S-T and Q-T, but not Q-U, are prolonged, causing an increased degree of merging between T and U. Three methods of differentiation between completely merged T and U waves and true T waves of long Q-T duration are given.
Problems in the Diagnosis and Surgical Treatment of Pulmonic Stenosis with Intact Ventricular Septum
Authors: KIRKLIN JOHN W. , CONNOLLY DANIEL C. , ELLIS F. HENRY , BURCHELL HOWARD B. , EDWARDS JESSE E. , WOOD EARL H.
Published: June 2012

Obstruction to pulmonary blood flow may occur in the pulmonic valve, in the infundibulum or in both. Cardiac catheterization aids in the determination of the site of obstruction. Criteria for the differentiation at operation of valvular and infundibular pulmonic stenosis are enumerated, and the usefulness of accurate pressure tracings during operation is emphasized. The accurate identification of the site or sites of obstruction to pulmonary blood flow is essential to proper surgical management. A correctly selected operation must be carried out in as complete a manner as possible.
The Treatment of Tuberculous Pericarditis
Authors: GOYETTE EDWIN M. , OVERHOLT EDWIN L. , RAPAPORT ELLIOTT
Published: June 2012

Twenty-seven patients with clinically primary tuberculous pericarditis were treated with prolonged chemotherapy consisting of intermittent doses of streptomycin and daily doses of paraminosalicylic acid or isoniazid. Twenty-one patients did well and were symptom-free six months to three years later. Five, one of whom died, developed constrictive pericarditis. Another died of widely disseminated tuberculosis.
Hemodynamic Studies of Patients with Myocardial Infarction
Authors: SMITH WARREN W. , WIKLER NORMAN S. , FOX ARTHUR C.
Published: June 2012

Cardiac output, venous and arterial pressure, total peripheral resistance and blood volume were measured in patients with acute myocardial infarction, with and without shock, and on recovery, and in patients without heart disease. Cardiac output falls to below normal after myocardial infarction, and rises significantly, though not always to normal, on recovery. Cardiac output was very low when myocardial infarction was complicated by shock. Fall of cardiac output to very low levels following myocardial infarction does not necessarily lead to development of shock. Venous pressure tended to be elevated in patients in shock as a result of myocardial infarction. Cardiac output was subnormal in patients with arteriosclerosis but without clinical heart disease: this was not attributable to reduced body oxygen consumption.
Constraining Wind Stress Products with Sea Surface Height Observations and Implications for Pacific Ocean Sea Level Trend Attribution*
Authors: McGregor Shayne , Gupta Alexander Sen , England Matthew H.
Published: June 2012

A number of global surface wind datasets are available that are commonly used to examine climate variability or trends and as boundary conditions for ocean circulation models. However, discrepancies exist among these products. This study uses observed Archiving, Validation, and Interpretation of Satellite Oceanographic (AVISO) sea surface height anomalies (SSHAs) as a means to help constrain the fidelity of these products in the tropical region. Each wind stress product is used to force a linear shallow water model (SWM) and the resulting hindcast thermocline depth anomalies are converted to SSHAs. The resulting SSHAs are then assessed to see how well they reproduce the dominant EOF modes of observed variability and the regional (global mean removed) sea level trend (1993–2007) in each of the three ocean basins. While the results suggest that all wind datasets reproduce the observed interannual variability with reasonable fidelity, the two SWM hindcasts that produce the observed linear trend with the highest fidelity are those incorporating interim ECMWF Re-Analysis (ERA-Interim) and Wave- and Anemometer-Based Sea Surface Wind (WASWind) forcing. The role of surface wind forcing (i.e., upper ocean heat content redistribution) versus global mean sea level change (i.e., including the additional contributions of glacier and ice sheet melt along with ocean thermal expansion) on the recent dramatic increase in western equatorial Pacific island sea level is then reassessed. The results suggest that the recent sea level increase cannot be explained solely by wind stress forcing, regardless of the dataset used; rather, the global mean sea level signal is required to fully explain this observed recent abrupt sea level rise and to better explain the sea level variability of the last 50–60 years.
The Role of Turbulent Mixing in an Overturning Circulation Maintained by Surface Buoyancy Forcing
Authors: Stewart Kial D. , Hughes Graham O. , Griffiths Ross W.
Published: June 2012

The role of externally imposed rates of small-scale mixing in an overturning circulation forced by differential surface buoyancy fluxes is examined in a laboratory experiment. The circulation occupies the full volume and involves a dense turbulent plume against the endwall and a broad upwelling throughout the interior. For strong externally imposed stirring, turbulent diffusion is the primary means of vertical density transport in the flow, and the dependence of the equilibrated circulation on the mixing rate accords with a theoretical model; the overturning rate increases as the ¼ power of the turbulent diffusivity. For weak externally imposed stirring, advection is the dominant mechanism of vertical density transport, and the circulation is independent of the rate of external stirring. The rate of vertical density transport is parameterized as a bulk diffusivity obtained from different methods, including one from a Munk-like advection–diffusion balance and another from the transport of buoyancy across the surface. For strong stirring, the bulk diffusivities returned by the various methods agree with the externally imposed mixing rate. However, the parameterizations implicitly include a nondiffusive component of vertical transport associated with advection of the density field and it is shown that, for weak stirring, the bulk diffusivities exceed the externally imposed mixing rate. For the oceans, results suggest that the primary effect of mixing (with energy sourced from winds, tides, and convection) is to deepen the thermocline, thereby influencing the entrainment and consequent vertical transport of density in the dense sinking regions. It is concluded that this advective transport of density, and not vertical mixing, is crucial for coupling the surface to the abyss.
Effect of binder metals on structure and properties of WC ceramic-metal composite coatings by laser-induction hybrid rapid cladding
Authors: Zhou Shengfeng , Dai Xiaoqin , Zhang Tianyou
Published: June 2012

In order to choose the appropriate binder metals for ceramic metal composite coating produced by laser-induction hybrid rapid cladding, the effect of binder metals on structure and properties of WC ceramic metal composite coatings were investigated. The maximum laser scanning speed and the maximum powder feeding rate of Ni-based + 50 wt.% WC composite coating can be increased to 1500 mm/min and 65.3 g/min, which are 1.5 and 1.23 times higher than those of Fe-based + 50 wt.% WC composite coating, respectively. Most of the WC particles are not dissolved completely and still preserve their eutectic structure in Ni-based metallic matrix, in which only a few of WC particles are completely dissolved and the carbides with dendritic and blocky shapes are dispersedly precipitated. However, WC particles are dissolved almost completely and the coarse herringbone M6C (M = W, Fe, Cr and Ni) eutectic carbides are precipitated in Fe-based metallic matrix. Moreover, the dissolution rate of WC in Fe-based alloy solvent is higher than that in Ni-based alloy solvent during laser-induction hybrid rapid cladding. The precipitation of coarse herringbone M6C carbides can accelerate the dissolution of WC during laser-induction hybrid rapid cladding. As a result, the microhardness and wear resistance of Ni-based WC composite coating are much higher than that of Fe-based WC composite coating.
Failure analysis of composite laminates subjected to hydrostatic stresses: A multicontinuum approach
Authors: Nelson Emmett E , Hansen Andrew C , Steven Mayes J
Published: June 2012

Triaxial failure analysis using multicontinuum decomposition has been employed at the constituent level to predict nonlinear damage behavior and failure envelopes, all involving through-thickness stresses. In addition, a structural analysis algorithm is presented and is found to be numerically highly efficient in that the relationships between composite properties and damaged or failed constituent properties are completely determined prior to structural analysis. As a part of the Second World-Wide Failure Exercise, three-dimensional failure envelopes and stress–strain curves involving isotropic materials as well various unidirectional and multi-directional materials are presented for 12 test cases requested by the organizers. The present paper provides new developments in the multicontinuum methodology including: (a) modification of the constituent failure criteria, (b) incorporation of pressure effects, (c) new damage analyses, and (d) implementation into a commercial finite element package. Correlation with experimental results is provided in a second article addressing Part B of the Second World-Wide Failure Exercise.
Reversal of Parenteral Nutrition–Associated Liver Disease With a Fish Oil–Based Lipid Emulsion (Omegaven) in an Adult Dependent on Home Parenteral Nutrition
Authors: Burns David L. , Gill Brian M.
Published: June 2012

Patients with intestinal failure and short bowel syndrome usually require chronic parenteral nutrition (PN). PN is associated with risks, including infections, vascular thrombosis, and liver disease. PN‐associated liver disease (PNALD) can progress from steatosis to chronic hepatitis and ultimately to cirrhosis. The etiology of PNALD is not completely understood. Therapies for PNALD include carbohydrate or lipid calorie reduction, antibiotics, or the use of ursodeoxycholic acid. When these efforts fail, therapeutic options are limited and liver transplantation may be required. The transition from a soybean‐ to a fish oil–based lipid formulation, such as the ω‐3 parenteral lipid formulation (Omegaven), has shown a dramatic reversal of PNALD within the pediatric population. This is the first report of a PN‐dependent adult in the United States complicated by PNALD and hepatic failure who had improvement of liver disease with an ω‐3 fish oil–based parenteral formulation.
Fusiform aneurysms of the vertebral artery: A hidden cause of exertional headache?
Authors: Mauri Gerard , Vega Pedro , Murias Eduardo , Vega Juan , Ramón César , Pascual Julio
Published: June 2012

Background: There is only one reported case of recurrent coital headache related to an unruptured saccular aneurysm of the carotid artery.

Case reports: We report on two cases of isolated recurrent coital/exertional headaches ipsilateral to unruptured fusiform aneurysms of the vertebral artery diagnosed by CT angiography. While one case is being managed conservatively, a vertebral stent has been set in the other.

Conclusions: CT angiography with full visualisation of intracranial and upper cervical arteries could be used as a screening diagnostic procedure in these cases. Together with saccular aneurysms, fusiform aneurysms should be added to the IHS classification as aetiology for exertional recurrent headaches.
The Development and Evaluation of Mutual Support Groups in Long-Term Care Homes
Authors: Theurer Kristine , Wister Andrew , Sixsmith Andrew , Chaudhury Habib , Lovegreen Loren
Published: June 2012

This article describes the development of a new mutual support group intervention for long-term care homes (LTCH); evaluates the processes, structure, and content of the intervention; and addresses replication and sustainability. Tom Kitwood’s model of personhood is used as the basis for developing a weekly discussion group using themes chosen by participants and theme-associated music, readings, and photographs. A mixed-methods qualitative process evaluation design encompasses focus groups, systematic observation of six resident groups, individual resident interviews ( N = 65), and staff interviews ( N = 7) in three LTCH in British Columbia, Canada. Resident reports and observations indicate positive benefits including a decrease in loneliness, the development of friendships, and increased coping skills, understanding, and support. Participating staff reported numerous benefits and described how the unique group structure fosters active participation of residents with moderate-severe cognitive impairment. This preliminary study suggests that mutual support groups have potential to offset loneliness, helplessness, and depression within LTCH.
Development of intra-vaginal matrices from polycaprolactone for sustained release of antimicrobial agents
Authors: Dang Nhung TT , Turner Mark S , Coombes Allan GA
Published: June 2012

Microporous poly(ɛ-caprolactone) matrices were loaded with an antibacterial agent, ciprofloxacin and an antifungal agent, miconazole nitrate, respectively, for investigations of their potential as controlled vaginal delivery devices. Ciprofloxacin loadings up to 15% w/w could be obtained by increasing the drug content of the poly(ɛ-caprolactone) solution, while the actual loadings of miconazole were much lower (1–3% w/w) due to drug partition into methanol during the solvent extraction. The kinetics of ciprofloxacin release in simulated vaginal fluid at 37℃ were characterised by a small burst release phase in the first 24 h, low drug release up to 7 days (10%) and gradual release of up to 80% of the drug content by day 30. Meanwhile, the release kinetics of miconazole-loaded matrices could be effectively described by the Higuchi model with 100% drug release from the highest loaded matrices (3.2% w/w) in 13 days. Ciprofloxacin or miconazole released over 30 and 13 days, respectively, from poly(ɛ-caprolactone) matrices into simulated vaginal fluid retained high levels of antimicrobial activity in excess of 80% of the activity of the free drug. This study confirms the potential of poly(ɛ-caprolactone) matrices for delivering antimicrobial agents in the form of an intra-vaginal device.
Antibiotic loading on bioactive glasses and glass-ceramics: An approach to surface modification
Authors: Miola Marta , Vitale-Brovarone Chiara , Mattu Clara , Verné Enrica
Published: June 2012

A bioactive glass and its corresponding glass-ceramic have been used to investigate the possibility to load a common antibiotic (carbenicillin) on their surface during the reactivity processes which occur by dipping these materials in a simulated body fluid. The materials bioactivity in the early stage of simulated body fluid treatment has been investigated by means of scanning electron microscopy (SEM-EDS) and X-ray diffraction. The uptake of carbenicillin has been performed by dipping the samples in simulated body fluid solution with a drug concentration of 500 mg/l for 6, 12 and 24 h. Some glass samples underwent a pre-treatment in simulated body fluid, for different time frames, in order to form a silica gel layer before the surface exposition to antibiotic. The carbenicillin release has been measured in water up to 36 h. The amount of incorporated and released antibiotic has been estimated by UV visible spectrophotometer. All samples were able to incorporate a significant amount of antibiotic and it was possible to tailor the drug release by modifying the simulated body fluid pre-treatment.
Urinary sediment ICAM-1 level in lupus nephritis
Authors: Guan J , Wang G , Tam L-S , Kwan BC-H , Li EK-M , Chow K-M , Li PK-T , Szeto C-C
Published: June 2012

Background: Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. Methods: The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. Results: LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) ( r = −0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 ( r = −0.591, p = 0.043) and miR-222 ( r = −0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level ( r = 0.658, p = 0.02). Conclusions: We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.
Actinides and radiation effects: impact on the back-end of the nuclear fuel cycle
Authors: Ewing R. C.
Published: June 2012

During the past 70 years, more than 2000 metric tonnes of Pu, and substantial quantities of the ‘minor’ actinides such as Np, Am and Cm, have been generated in nuclear reactors. Some of these transuranium elements can be a source of energy in fission reactions (e.g.239Pu), a source of fissile material for nuclear weapons (e.g.239Pu and2Np), and of environmental concern because of their long half-lives and radiotoxicity (e.g.239Pu and237Np). There are two basic strategies for the disposition of these transuranium elements: (1) to ‘burn’ or fission the actinides using nuclear reactors or accelerators; (2) to dispose of the actinides directly as spent nuclear fuel or to ‘sequester’ the actinides in chemically durable, radiation-resistant materials that are also suitable for geological disposal. For the latter strategy, there has been substantial interest in the use of actinide-bearing minerals, especially isometric pyrochlore,A2B2Oi (A =rare earths;B =Ti, Zr, Sn, Hf), for the immobilization of actinides, particularly plutonium, both as inert matrix fuels and nuclear waste forms. Systematic studies of rare-earth pyrochlores have led to the discovery that certain compositions(B =Zr, Hf) are stable to very high doses of α-decay event damage. Recent developments in the understanding of the properties of actinide-bearing solids have opened up new possibilities for the design of advanced nuclear materials that can be used as fuels and waste forms. As an example, the amount of radiation damage that accumulates over time can be controlled by the selection of an appropriate composition for the pyrochlore and a consideration of the thermal environment of disposal. In the case of deep borehole disposal (3—5 km), the natural geothermal gradient may provide enough heat to reduce the amount of accumulated radiation damage by thermal annealing.
Recrystallization of metamict allanite
Authors: Beirau T. , Paulmann C. , Bismayer U.
Published: June 2012

Allanite is a common accessory mineral in igneous rocks. Allanite becomes metamict over geological time-scales as a result of the α-decay of radioactive elements in the crystal structure. This study focuses on the recrystallization of metamict allanite from Savvushka, Russia. The structural recovery produced by annealing was investigated by X-ray powder diffraction, single-crystal synchrotron X-ray diffraction and infrared spectroscopy. A kinetic analysis is presented that shows that the recrystallization process proceeds by at least two different mechanisms.
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1
Authors: Fang Jing , Rhyasen Garrett , Bolanos Lyndsey , Rasch Christopher , Varney Melinda , Wunderlich Mark , Goyama Susumu , Jansen Gerrit , Cloos Jacqueline , Rigolino Carmela , Cortelezzi Agostino , Mulloy James C. , Oliva Esther N. , Cuzzola Maria , Starczynowski Daniel T.
Published: June 2012

Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that bortezomib induces proteasome-independent degradation of the TRAF6 protein, but not mRNA, in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of bortezomib due to down-regulation of the proteasomal subunit α-1 (PSMA1). To determine the molecular consequences of loss of TRAF6 in MDS/AML cells, in the present study, we applied gene-expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe herein novel mechanisms by which TRAF6 is regulated through bortezomib/autophagy–mediated degradation and by which it alters MDS/AML sensitivity to bortezomib by controlling PSMA1 expression.
Micronutrient deficiency in obese subjects undergoing low calorie diet
Authors: Damms-Machado Antje , Weser Gesine , Bischoff Stephan C
Published: June 2012

Background

The prevalence of micronutrient deficiencies is higher in obese individuals compared to normal-weight people, probably because of inadequate eating habits but also due to increased demands among overweight persons, which are underestimated by dietary reference intakes (DRI) intended for the general population. We therefore evaluated the dietary micronutrient intake in obese individuals compared to a reference population and DRI recommendations. Furthermore, we determined the micronutrient status in obese subjects undergoing a standardized DRI-covering low-calorie formula diet to analyze if the DRI meet the micronutrient requirements of obese individuals.

Methods

In 104 subjects baseline micronutrient intake was determined by dietary record collection. A randomly assigned subgroup of subjects (n = 32) underwent a standardized DRI-covering low-calorie formula diet over a period of three months. Pre- and post-interventional intracellular micronutrient status in buccal mucosa cells (BMC) was analyzed, as well as additional micronutrient serum concentrations in 14 of the subjects.

Results

Prior to dietetic intervention, nutrition was calorie-rich and micronutrient-poor. Baseline deficiencies in serum concentrations were observed for 25-hydroxyvitamin-D, vitamin C, selenium, iron, as well as ß-carotene, vitamin C, and lycopene in BMC. After a three-month period of formula diet even more subjects had reduced micronutrient levels of vitamin C (serum, BMC), zinc, and lycopene. There was a significant negative correlation between lipophilic serum vitamin concentrations and body fat, as well as between iron and C-reactive protein.

Conclusions

The present pilot study shows that micronutrient deficiency occurring in obese individuals is not corrected by protein-rich formula diet containing vitamins and minerals according to DRI. In contrast, micronutrient levels remain low or become even lower, which might be explained by insufficient intake, increased demand and unbalanced dispersal of lipophilic compounds in the body.

Trial registration

The study was registered at ClinicalTrials.gov (NCT01344525). The study protocol comprises only a part of the approved trial protocol.
Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages
Authors: Movita Dowty , Kreefft Kim , Biesta Paula , van Oudenaren Adri , Leenen Pieter J M , Janssen Harry L A , Boonstra Andre
Published: June 2012

Kupffer cells are endocytic, yet weak producers of proinflammatory cytokines, as compared against splenic and peritoneal macrophages.

The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady-state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL-10, low or undetectable levels of IL-12p40 and TNF, and up-regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL-12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady-state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.
Greece, Turkey, and NATO
Authors: Binder David
Published: June 2012

The North Atlantic Treaty Organization has some strange partners, in terms of history. The oddest couple of all may be Greece and Turkey. The two neighbors fought four wars in the space of a quarter century (1897 to 1922) and are still mutually suspicious. But they have followed parallel courses within the alliance—joining some group actions while remaining aloof to others. Meanwhile, the alliance has over the past two decades changed its posture from defense to offense and from a focus on the European continent to perceived enemies in North Africa, Asia, and the Middle East. Now it is a heavily armed organization in almost desperate search of an antagonist. That is not what Greece or Turkey signed up for when they joined NATO in 1952.
Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering
Authors: Langford Peter R. , Keyes Lance , Hansen Marc D. H.
Published: June 2012

Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and migrating as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. Here we apply a chemical biology approach to identify components of HGF signaling that are required for scattering in an in vitro model system. This approach yields a number of small molecules that block HGF-induced scattering, including a calcium channel blocker. We show that HGF stimulation results in sudden and transient increases in ion channel influxes at the plasma membrane. Though multiple channels occur in the membranes of our model system, we find that TrpC6 is specifically required for HGF-induced scattering. We further demonstrate that HGF-induced ion influxes through TrpC6 channels coincide with a transient increase in NFAT-dependent gene transcription and that NFAT-dependent gene transcription is required for HGF-induced cell scattering.
APPL1 regulates basal NF-κB activity by stabilizing NIK
Authors: Hupalowska Anna , Pyrzynska Beata , Miaczynska Marta
Published: June 2012

APPL1 is a multifunctional adaptor protein that binds membrane receptors, signaling proteins and nuclear factors, thereby acting in endosomal trafficking and in different signaling pathways. Here we uncover a novel role of APPL1 as a positive regulator of transcriptional activity of NF-κB under basal but not TNFα-stimulated conditions. APPL1 was found to directly interact with TRAF2, an adaptor protein known to activate the canonical NF-κB signaling. APPL1 synergized with TRAF2 to induce NF-κB activation and both proteins were necessary for this process by functioning upstream of the IKK complex. Although TRAF2 was not detectable on APPL endosomes, endosomal recruitment of APPL1 was required for its function in the NF-κB pathway. Importantly, in the canonical pathway APPL1 appeared to regulate the proper spatial distribution of p65 in the absence of cytokine stimulation, since its overexpression enhanced and its depletion reduced the nuclear accumulation of p65. Analyzing the patterns of gene transcription upon APPL1 overproduction or depletion we found altered expression of NF-κB target genes encoding cytokines. At the molecular level, overexpressed APPL1 markedly increased the level of NIK, the key component of the noncanonical NF-κB pathway, by reducing its association with the degradative complex containing TRAF2, TRAF3 and cIAP1. In turn, high levels of NIK triggered nuclear translocation of p65. Collectively, we propose that APPL1 regulates basal NF-κB activity by modulating the stability of NIK, which affects the activation of p65. This places APPL1 as a novel link between the canonical and noncanonical machineries of NF-κB activation.
Can fiscal sovereignty be reconciled with fiscal discipline?
Authors: Kopits George
Published: June 2012

Over the past two decades, international bond markets have become the chief disciplinarian of fiscal policy, displacing the International Monetary Fund and the European Union in this role. This trend culminated in the wake of the global financial crisis, as countries that had indulged in moral hazard and fiscal profligacy during the Great Moderation were vulnerable to a sharp rise in sovereign risk premium and in some cases to loss of market access. The article compares the response of new governments in Hungary and United Kingdom to restore policy credibility. A major lesson is that governments that adopt a rules-based fiscal framework, including fiscal watchdogs and transparency norms, are far more successful in anchoring fiscal expectations and in achieving fiscal sovereignty than those that do not.
The effects of the economic crisis on income convergence in the European Union
Authors: Stanišić Nenad
Published: June 2012

This paper evaluates income convergence in the European Union, between “old” (EU15) and “new” member states from Central and East Europe (CEE10), and among the countries within these two groups. The GDP per capita convergence should be expected according to the exogenous economic growth model and neoclassical trade theory. The presence ofσ-convergence and both absolute and conditionalβ-convergence is tested for on a sample of 25 European Union countries (EU25). Results confirm the existence ofβ-convergence of GDP per capita at purchasing power parity among EU25, but not among EU15 and CEE10 countries.σ-convergence has been confirmed among EU25 and CEE10 countries, while GDP per capita has been diverging in the EU15 group of countries. Moreover, the results reveal that recent economic crisis has reversed long-term tendencies and led to income convergence within EU15 and divergence within CEE10. During the crisis, the income differences among the EU25 countries have increased, but the scope and duration of this effect has been limited and has not affected the long term convergence path. However, the obtained long term speed of convergence is significantly lower compared with the previous researches.
Medical Histories: A Case Report of Pharmacovigilance in Supporting Dentists and Participation in a Drug‐Safety Program
Authors: Karl Edward H. , Curro Frederick A.
Published: June 2012

Introduction: Antibiotics are a class of medications widely used by dentists. The class of agents has a number of listed side effects. This case report details an unusual adverse effect of tetracycline‐induced psychosis recognized due to the diligence of a practitioner. To our knowledge, this is the first reported case by a dentist.

Case Presentation: A 44‐year‐old patient was started on tetracycline therapy for prophylaxis before a periodontal procedure. The patient began having paranoid and psychotic experiences. The patient sought psychiatric medical care and was diagnosed with tetracycline‐induced psychosis. He was treated with an antipsychotic drug, which resolved his symptoms.

Conclusion: Dental medical histories are a resource that is underused and can often be of value in the continual assessment of drug safety and pharmacovigilance.
How to Select Replacement Grafts for Various Periodontal and Implant Indications
Authors: Hsu Yung‐Ting , Wang Hom‐Lay
Published: June 2012

Focused Clinical Question: How are bone replacement grafts for various periodontal and implant indications properly selected?

Summary: The purpose of this paper is to review the properties of available bone replacement materials and provide guidelines of how to choose certain graft materials for different clinical indications (e.g., periodontal defects, peri‐implant defects, socket augmentation, ridge augmentation, and sinus augmentation).

Conclusion: Full understanding of material properties and meticulous case selection may help to maximize the benefit of bone replacement grafts in tooth‐ and implant‐related regeneration.
Implant Site Development With Simultaneous Block and Soft‐Tissue Graft
Authors: Fagan Mark C. , Conte Gregory J. , Kao Richard T.
Published: June 2012

Introduction: Reconstruction of lost alveolar bone for future implant placement has been accomplished through bone grafts, used alone or in combination with a barrier membrane. Although effective in fulfilling the hard‐tissue requirements, soft‐tissue augmentation is often necessary and requires a supplemental surgical procedure. The interpositional vascularized augmentation neogenesis (IVAN) technique has been shown to be effective in simultaneously grafting both hard and soft tissues in both immediate and delayed implant placements. One reason for the success of the cases presented in the previous IVAN articles was as a result of the presence of mesial and distal walls of the extraction sockets that helped to maintain space under the guided bone membrane. In cases in which the grafted site has minimal walls to aid in space maintenance, a more rigid graft, block type, is desirable.

Case Presentation: In this case report, modification of the IVAN technique to use block bone allograft (BBA) in conjunction with pediculated connective tissue graft (PCTG) to simultaneously augment both the hard and soft tissue at time of tooth extraction is reported.

Conclusions: This approach can be used effectively to simultaneously augment hard and soft tissue by using BBA and PCTG to correct large three‐dimensional defects. This approach is advantageous in that it can correct defects in which bone grafts used alone or in combination with a barrier membrane is not predictable.
Magnesium salts as compounds of the preparation of magnesium oxide from Tunisian natural brines
Authors: Behij Souheil , Hammi Halim , Hamzaoui Hichem , M’nif Adel
Published: June 2012

Magnesium oxide is one of the most important magnesium compounds used in
industry. The production of MgO is often done from calcined magnesium
carbonate or from natural magnesium saline solutions (sea water and brines).
In the case of these solutions, magnesium oxide is precipitated after the
addition of a strong base (eg. Ammonia). Magnesium hydroxide is calcined
after its separation from the excess resulting from the strong base through
filtration. Thus, magnesia qualities may differ depending on several physical
parameters and particularly on the nature of the compound. Consequently, two
different compounds were selected: magnesium chloride and magnesium sulphate
which can be recovered from Tunisian natural brines. Three physical factors
were considered: calcination temperatures, precipitation temperatures and
calcination time of Mg(OH)2. The decomposition of Mg(OH)2 was investigated by
DTA/TGA. Mass losses vary in the range (23.0%-29.9%). Starting decomposition
temperatures are between 362?C and 385?C. The MgO produced from MgSO4 under
1000?C within 48 hours of calcination time and with 40?C as a reaction
temperature for Mg(OH)2 shows a good crystallinity and is of a cristallyte
size of 86.3 nm and has a specific surface area equal to 16.87 m2g-1.
Finally, morphological differences between MgO agglomerates at different
temperatures were observed by SEM. Consequently, magnesium sulphate as
precursor for preparing MgO is selected.
Modern trends in the development of agriculture and demands on plant breeding and soil management
Authors: Kovacevic Dusan , Lazic Branka
Published: June 2012

Agriculture is usually developed as much and just society where there is a
branch of the economy. Today, there are different directions from industry
agriculture to many concepts based on ecological principles. Future of
agriculture development in the XXI century will imply sustainable agriculture
as the alternative to the industrial agriculture. Conventional agriculture as
an intensive one has a duty to ensure maximum production in terms of quantity
and quality with the low cost. For this purpose we have many cultural
practices, sometimes in addition to the expected positive but sometimes with
many unexpected long-term negative effects in agroecosystems. Organic
agriculture is one of the most interesting current trends in agriculture
completely based on strong ecological principles and the absence of
application of agrochemicals (pesticides, fertilizers, hormones), GMO, etc.
Organic agriculture is a holistic way of farming: besides production of goods
of high quality (better flavor, high content dry matter, vitamins,
antioxidants); conservation of the natural resources (soil, water) and
richness of biodiversity.