Single-photon ionization of SiC in the gas phase: experimental and ab initio characterization of SiC.
We report the first experimental observation of single-photon ionization transitions of the SiC radical between 8.0 and 11.0 eV performed on the DESIRS beamline at the SOLEIL synchrotron facility. The SiC radical, very difficult to synthesize in the gas phase, was produced through chemical reactions between CHx (x = 0-3) and SiHy (y = 0-3) in a continuous microwave discharge flow tube, the CHx and SiHy species being formed by successive hydrogen-atom abstractions induced by fluorine atoms on methane and silane, respectively. Mass-selected ion yield and photoelectron spectra were recorded as a function of photon energy using a double imaging photoelectron/photoion coincidence spectrometer. The photoelectron spectrum enables the first direct experimental determinations of the X+ 4Σ- ← X 3Π and 1+ 2Π ← X 3Π adiabatic ionization energies of SiC (8.978(10) eV and 10.216(24) eV, respectively). Calculated spectra based on Franck-Condon factors are compared with the experimental spectra. These spectra were obtained by solving the rovibrational Hamiltonian, using the potential energy curves calculated at the multireference single and double configuration interaction level with Davidson correction (MRCI + Q) and the aug-cc-pV5Z basis set. MRCI + Q calculations including the core and core-valence electron correlation were performed using the aug-cc-pCV6Z basis set to predict the spectroscopic properties of the six lowest electronic states of SiC+. Complete basis set extrapolations and relativistic energy corrections were also included in the determination of the energy differences characterizing the photoionization process. Using our experimental and theoretical results, we derived semi-experimental values for the five lowest ionization energies of SiC.


Rapid, simple bioassay for 5-fluorocytosine in the presence of amphotericin B.
It is important that serum levels of 5-fluorocytosine (5FC) be measured to insure therapeutic levels while avoiding toxicity. This is particularly true in patients with renal insufficiency. The concurrent use of amphotericin B and 5FC complicates the measurement of 5FC in the serum, since fungi used in conventional bioassay systems are uniformly susceptible to amphotericin B. This paper describes the development of a simple, reliable, 6-h bioassay for 5FC in the presence of amphotericin B. The assay is based upon the fact that 5FC diffuses readily through yeast nitrogen base agar, whereas amphotericin B apparently does not. This assay allows rapid adjustments in therapy of patients receiving both 5FC and amphotericin B and has permitted us to maintain 5FC serum levels between limits of 25 and 120 mug/ml in patients with altered renal function.


Sudden death among postoperative patients with tetralogy of Fallot: a follow-up study of 243 patients for an average of twelve years.
Two hundred and forty-three patients were evaluated following total correction of tetralogy of Fallot with special emphasis on postoperative conduction disturbances and on the occurrence of sudden death. The average follow-up period was 12 years with a range of 6 1/2 to 16 1/2 years. Sudden death occurred in seven patients. Four deaths were among those with right bundle branch block pattern (RBBB) and three of the four had premature ventricular contractions (PVC) for more than one month postoperatively. PVCs were documented in ten of the 158 patients with RBBB; sudden death occurred in three (30%). Three of the ten (30%) patients with trifascicular block pattern (TB) died suddenly, while no deaths occurred in 24 patients with bifascicular block pattern (BB). Progression of RBBB to BB and TB occurred in 18 patients from one month to seven years postoperatively (58% of BB and 40% of TB). The risk of sudden death in patients with RBBB and PVCs following tetralogy repair is high and warrants consideration of suppressive therapy. TB also carries a high risk. The finding that RBBB may progress to BB or TB mandates long-term careful follow-up of all tetralogy patients with postoperative conduction disturbances.


Palladium-catalyzed asymmetric cycloadditions of vinylcyclopropanes and in situ formed unsaturated imines: construction of structurally and optically enriched spiroindolenines.
A palladium-catalyzed (3 + 2) cycloaddition of vinyl cyclopropane and α,β-unsaturated imines generated in situ from aryl sulfonyl indoles is reported. The reaction proceeds with high diastereoselectivity to provide the optically enriched spirocyclopentane-1,3'-indolenines in up to 74% yield and with up to 97% ee, which contains an all-carbon quaternary center and two tertiary stereocenters. The reaction involves a first conjugate addition of the carbon anion of zwitterionic π-allylpalladium complex from vinyl cyclopropane to the in situ formed unsaturated imine followed by a palladium-catalyzed intramolecular C3-allylation of indole.


Criteria for the safe discharge of patients from the recovery room.
Guidelines need to be in place to help nurses in the recovery room make appropriate and safe decisions when discharging patients to a surgical ward. Consciousness level, respiration, circulation, pain control, homeostasis and wound care should all be considered. Criteria from the Freeman Hospital provides practical guidance.


Spontaneous Spinal Epidural Hematoma Associated With the Use of Low-dose Aspirin in Elderly Patient.
Spontaneous spinal epidural hematoma is a rare condition defined by bleeding in the epidural space of the spine with no identifiable causes such as trauma, vascular malformation, or bleeding disorders. This is a case of a 79-year-old woman with a medical history of diabetes mellitus, dyslipidemia, and hypertension presented with the sudden onset of severe thoracolumbar back pain associated with weakness and numbness in her bilateral lower limb. Examination of the lower limb showed bilateral lower limb motor and sensory deficits. Laboratory investigations showed normal results. MRI showed posterior extradural intraspinal hematoma from T11 to L3 vertebrae. Patient underwent right hemilaminectomy and posterior decompression of T12 and L1 vertebrae to evacuate the hematoma. Postoperatively, her neurologic complications improved gradually. Decision was made not to restart aspirin. On follow-up at 1 year, the patient had complete recovery of neurologic complications of both lower limb and had no recurrence of bleeding. In short, this is a case of spontaneous spinal epidural hematoma associated with long-term use of low-dose aspirin in an elderly patient requiring surgical evacuation of hematoma with good functional outcome after the surgery. Therefore, aspirin should be prescribed cautiously especially to elderly patients.


Infection of neutrophil granulocytes with Leishmania major activates ERK 1/2 and modulates multiple apoptotic pathways to inhibit apoptosis.
Neutrophil granulocytes provide the first line of defense against bacterial, fungal, and parasitic infections. They phagocytose and kill many invading pathogens. Certain pathogenic microorganisms such as the intracellular protozoan parasite Leishmania major (L. major) can survive inside neutrophils. Mature neutrophils have a very short life span due to spontaneous apoptosis. Previously, we have reported that infections with L. major are able to delay spontaneous apoptosis. In the present study, we addressed the underlying mechanisms of regulation of both extrinsic and intrinsic apoptosis. We show that interaction with L. major transiently activates ERK1/2 phosphorylation. Pharmacological inhibition of ERK1/2 phosphorylation reversed the apoptosis delay. Moreover, infection leads to the enhanced and sustainable expression of the anti-apoptotic proteins Bcl-2 and Bfl-1, respectively. As downstream events, the release of cytochrome c from mitochondria and processing of caspase-6 were inhibited. We also confirm that infection with L. major results in reduced FAS expression on the surface of neutrophils. The presented data indicate that infection with L. major affects both intrinsic as well as extrinsic pathways of neutrophil apoptosis. Enhanced life span of host neutrophils enables the parasite to survive within neutrophils.


Spatial analysis of body mass index and smoking behavior among WISEWOMAN participants.
The WISEWOMAN program focuses on reducing cardiovascular disease (CVD) risk factors by providing screening and lifestyle interventions for many low-income and uninsured women. To provide the most effective interventions possible, it is important to understand the characteristics of WISEWOMAN participants and their communities. We used baseline data collected for WISEWOMAN participants from five states (Connecticut, Michigan, Nebraska, North Carolina, and South Dakota) who had enrolled in WISEWOMAN between January 2001 and December 2002 in order to examine body mass index (BMI) and smoking behavior for evidence of spatial clustering. We then examined whether neighborhood characteristics in clusters of high-risk factors differed from neighborhood characteristics in other locations. Six percent of the WISEWOMAN participants lived in ZIP codes with high-BMI clusters, and 4% lived in ZIP codes with high-smoking clusters. High-BMI and high-smoking clusters occurred, however, in different locations from each other. The high-BMI-clustered ZIP codes were, on average, located in more disadvantaged areas. Most of the differences between the high-smoking-clustered ZIP codes and the remaining ZIP codes were not statistically significant. Our analysis revealed spatial clustering in CVD risk factors among WISE-WOMAN participants. We also found evidence of a correlation between high-BMI clusters and low socioeconomic status of the surrounding community. A more in-depth analysis of the relationship between risk factors (e.g., BMI) and community characteristics in clustered locations will provide further information concerning the role of the community in affecting individual behavior and should allow for tailoring interventions to reduce these risk factors more effectively.


Extensive mass spectrometry-based analysis of the fission yeast proteome: the Schizosaccharomyces pombe PeptideAtlas.
We report a high quality and system-wide proteome catalogue covering 71% (3,542 proteins) of the predicted genes of fission yeast, Schizosaccharomyces pombe, presenting the largest protein dataset to date for this important model organism. We obtained this high proteome and peptide (11.4 peptides/protein) coverage by a combination of extensive sample fractionation, high resolution Orbitrap mass spectrometry, and combined database searching using the iProphet software as part of the Trans-Proteomics Pipeline. All raw and processed data are made accessible in the S. pombe PeptideAtlas. The identified proteins showed no biases in functional properties and allowed global estimation of protein abundances. The high coverage of the PeptideAtlas allowed correlation with transcriptomic data in a system-wide manner indicating that post-transcriptional processes control the levels of at least half of all identified proteins. Interestingly, the correlation was not equally tight for all functional categories ranging from r(s) >0.80 for proteins involved in translation to r(s) <0.45 for signal transduction proteins. Moreover, many proteins involved in DNA damage repair could not be detected in the PeptideAtlas despite their high mRNA levels, strengthening the translation-on-demand hypothesis for members of this protein class. In summary, the extensive and publicly available S. pombe PeptideAtlas together with the generated proteotypic peptide spectral library will be a useful resource for future targeted, in-depth, and quantitative proteomic studies on this microorganism.


Light dependence of [3H]leucine incorporation in the oligotrophic North Pacific ocean.
The influence of irradiance on bacterial incorporation of [(3)H]leucine was evaluated at Station ALOHA in the oligotrophic North Pacific subtropical gyre. Six experiments were conducted on three cruises to Station ALOHA to examine how [(3)H]leucine incorporation varied as a function of irradiance. Two experiments were also conducted to assess the photoautotrophic response to irradiance (based on photosynthetic uptake of [(14)C]bicarbonate) in both the upper and lower photic zones. Rates of [(3)H]leucine incorporation responded to irradiance in a photosynthesis-like manner, increasing sharply at low light and then saturating and sometimes declining with increasing light intensity. The influence of irradiance on bacterial growth was evaluated in both the well-lit (5 to 25 m) and dimly lit regions of the upper ocean (75 to 100 m) to determine whether the bacterial response to irradiance differed along the depth-dependent light gradient of the photic zone. [(3)H]leucine incorporation rates were analyzed with a photosynthesis-irradiance model for a quantitative description of the relationships between [(3)H]leucine incorporation and irradiance. Maximum rates of [(3)H]leucine incorporation in the upper photic zone increased 48 to 92% relative to those of dark-incubated samples, with [(3)H]leucine incorporation saturating at light intensities between 58 and 363 micromol of quanta m(-2) s(-1). Rates of [(3)H]leucine incorporation in the deep photic zone were photostimulated 53 to 114% and were susceptible to photoinhibition, with rates declining at light intensities of >100 micromol of quanta m(-2) s(-1). The results of these experiments revealed that sunlight directly influences bacterial growth in this open-ocean ecosystem.


Three years follow-up of panic disorder patients: a naturalistic study.
Forty Danish panic disorder patients participating in a placebo controlled study of alprazolam and imipramine (The Cross National Collaborative Panic Study, Phase II) were followed up by a telephone interview three years later, with essentially the same battery of evaluation procedures applied at baseline, end of study, and follow-up. The main finding was that panic disorder is a chronic disorder, but fluctuating in form and severity in the course of time. Twenty-five percent of the patients no longer fulfilled the DSM-III criteria for panic disorder, but had substantial disability due to a variety of symptoms, including panic attacks at infrequent rate, generalized anxiety symptoms, affective symptoms, and phobic avoidance behavior. Nearly three fourths of the patients were under treatment at follow-up. Benzodiazepines were the drugs most often prescribed, usually in combination with supportive psychotherapy. It was concluded that the different types of treatment offered were insufficient. Variables predicting panic disorder or substantial disability at 3-years follow-up were few.


Quantitative Proteomics Reveals Differences in the Response of Neutrophils Isolated from Healthy or Diabetic Subjects to Infection with Capsule-Variant Burkholderia thailandensis.
In Thailand, diabetes mellitus is the most significant risk factor for melioidosis, a severe disease caused by Burkholderia pseudomallei. In this study, neutrophils isolated from healthy or diabetic subjects were infected with B. thailandensis E555, a variant strain with a B. pseudomallei-like capsular polysaccharide used here as a surrogate micro-organism for B. pseudomallei. At 2 h post-infection, neutrophil proteins were subjected to 4-plex iTRAQ-based comparative proteomic analysis. A total of 341 proteins were identified in two or more samples, of which several proteins involved in oxidative stress and inflammation were enriched in infected diabetic neutrophils. We validated this finding by demonstrating that infected diabetic neutrophils generated significantly elevated levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β, and IL-17 compared to healthy neutrophils. Our data also revealed that infected neutrophils from healthy or diabetic individuals undergo apoptotic cell death at distinctly different rates, with infected diabetic neutrophils showing a diminished ability to delay apoptosis and an increased likelihood of undergoing a lytic form of cell death, compared to infected neutrophils from healthy individuals. Increased expression of inflammatory proteins by infected neutrophils could contribute to the increased susceptibility to infection and inflammation in diabetic patients in melioidosis-endemic areas.


Cyclosporin-induced gingival overgrowth in children.
Cyclosporin is a potent immunosuppressant drug commonly used to prevent organ transplant rejection. In recent years, there has been a widening of its therapeutic use and an increase in the number of patients undergoing transplantation. Gingival overgrowth is one of several oral side-effects of cyclosporin, with a quoted prevalence of between 8% and 100%. There is continued debate over the factors which modify the degree of overgrowth, including individual sensitivity, age, dose of drug, duration of drug therapy and the presence of dental plaque. The exact mechanism of gingival overgrowth is still being debated, but appears to be caused by a combination of the proliferation of fibroblasts within the gingival tissue, an increase in the deposition of collagen and extracellular matrix, and a decrease in phagocytosis with a net gain in gingival tissue mass. A number of treatment options are utilized in the treatment of gingival overgrowth, including CO2 laser surgery, improved oral hygiene, the use of antibiotics such as metronidazole and azithromycin, and surgical intervention. In the clinical application of cyclosporin, there is little correlation between cyclosporin dose, serum trough levels and total exposure to the drug, making it difficult to achieve the desired therapeutic response. These problems were previously further complicated by the variability of absorption of the drug via the gastrointestinal tract. The original cyclosporin formulation, Sandimmune, was replaced by a new formulation, Neoral, which has a more reliable absorption, and gives a closer correlation between trough concentration levels and individual bioavailability. There is a conflict of opinion over whether or not the side-effect profile of Neoral varies from its precursor Sandimmune. It has yet to be seen whether the increased bioavailability of Neoral will result in an increased severity and prevalence of gingival overgrowth. An alternative immunosuppressant drug, tacrolimus, which is a macrolide antibiotic with a different side-effect profile, has emerged as a substitute for cyclosporin in organ transplantation. However, there have been conflicting reports of its side-effects and its capacity to cause gingival overgrowth.


A radioreceptor assay for insulin: direct measurement of human serum insulin.
A simple radioreceptor assay was established with sensitivity and accuracy sufficient to detect concentrations of insulin in human peripheral sera. The radioreceptor assay was carried out at 4 degrees C using rabbit erythrocyte membranes and 125I-insulin. In the absence of native insulin, approximately 31% of the total 125I-insulin concentration was bound to erythrocyte membranes. Fourty-six per cent of this binding was displaced by 312 microunits/ml of native insulin. The precision expressed as coefficient of variation was 3 to 21% of the mean for the within-assay, and 1 to 21% for the between-assay, respectively. The recovery of standard porcine insulin added to the serum was 105% on the average. Insulin values in 24 samples of human sera measured by the present assay agreed well with immunoreactive insulin values.


[Construction of a Risk Prediction Model for Lung Cancer Based on Lifestyle Behaviors in the UK Biobank Large-Scale Population Cohort].
To identify the risk factors related to lifestyle behaviors that affect the incidence of lung cancer, to build a lung cancer risk prediction model to identify, in the population, individuals who are at high risk, and to facilitate the early detection of lung cancer. The data used in the study were obtained from the UK Biobank, a database that contains information collected from 502 389 participants between March 2006 and October 2010. Based on domestic and international guidelines for lung cancer screening and high-quality research literature on lung cancer risk factors, high-risk population identification criteria were determined. Univariate Cox regression was performed to screen for risk factors of lung cancer and a multifactor lung cancer risk prediction model was constructed using Cox proportional hazards regression. Based on the comparison of Akaike information criterion and Schoenfeld residual test results, the optimal fitted model assuming proportional hazards was selected. The multiple factor Cox proportional hazards regression was performed to consider the survival time and the population was randomly divided into a training set and a validation set by a ratio of 7:3. The model was built using the training set and the performance of the model was internally validated using the validation set. The area under the receiver operating characteristic (ROC) curve ( AUC) was used to evaluate the efficacy of the model. The population was categorized into low-risk, moderate-risk, and high-risk groups based on the probability of occurrence of 0% to <25%, 25% to <75%, and 75% to 100%. The respective proportions of affected individuals in each risk group were calculated. The study eventually covered 453 558 individuals, and out of the cumulative follow-up of 5 505 402 person-years, a total of 2 330 cases of lung cancer were diagnosed. Cox proportional hazards regression was performed to identify 10 independent variables as predictors of lung cancer, including age, body mass index (BMI), education, income, physical activity, smoking status, alcohol consumption frequency, fresh fruit intake, family history of cancer, and tobacco exposure, and a model was established accordingly. Internal validation results showed that 8 independent variables (all the 10 independent variables screened out except for BMI and fresh fruit intake) were significant influencing factors of lung cancer ( P<0.05). The AUC of the training set for predicting lung cancer occurrence at one year, five years, and ten years were 0.825, 0.785, and 0.777, respectively. The AUC of the validation set for predicting lung cancer occurrence at one year, five years, and ten years were 0.857, 0.782, and 0.765, respectively. 68.38% of the individuals who might develop lung cancer in the future could be identified by screening the high-risk population. We established, in this study, a model for predicting lung cancer risks associated with lifestyle behaviors of a large population. Showing good performance in discriminatory ability, the model can be used as a tool for developing standardized screening strategies for lung cancer.


The nonsurgical management of odontoid fractures in adults.
Twenty-five odontoid fractures that were treated nonsurgically at the University of Virginia Hospital in the last 5 years were reviewed. Motor vehicle accidents were the major cause of this injury in our series. Early recognition and firm external stabilization of Type I and Type III fractures of the odontoid resulted in union in 100% of our patients. There were 12 Type II fractures with a nonunion rate of 42%. Thus, an overall rate of union of 80% was obtained. It is suggested in the literature and by this series that early recognition, reduction, and rigid external immobilization of Types I and III fractures of the odontoid should promote bony union. Type II fractures may also be managed successfully by closed methods, although the outcome is less certain.


[Survey of coronary stents development for restenosis prevention].
Coronary stents are playing an effective way of curing cardiovascular diseases while a major drawback of restenosis is in general still present. Restenosis is resulting from neointimal hyperplasia and thrombosis which induced by the vascular lesion, hemodynamic modification and the reduction or oscillation of wall shear stress (WSS). The crucial factors that would determine the restenosis were reviewed in this paper, including the material bio-compatibilities, surface treatments, stent configuration designs and hemodynamics analyses. In particular, the hemodynamics after stents implantation based on in vivo, in vitro or Computational Fluid Dynamics (CFD) methods was discussed. A novel CFD and experimental approach of dynamics in the stent-vascular coupling system was proposed.


[Effect of antitubercular preparations on the function of the ciliary epithelium of the respiratory tract mucosa].
The effect of various concentrations of streptomycin, isoniazid, rifampicin and ethambutol on the function of the siliated epithelium of the frog oral mucosa was studied (110 experiments with 50 frogs). The level of inhibition of the siliated epithelium function depended on the properties of the drugs and their concentration in solution. More pronounced inhibition was induced by 15 per cent ethambutol solution and 10 per cent isoniazid solution. The least inhibition of the siliated epithelium function was observed with the use of 6.25 per cent streptomycin solution, 5 per cent isoniazid solution, 7.5 per cent ethambutol solution and 3.75 per cent rifampicin solution.


beta 2-Glycoprotein I reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome.
To elucidate the specificity of anticardiolipin antibodies (aCL) from patients with the antiphospholipid syndrome (APS) to various phospholipids (PLs), DNA, and beta 2-glycoprotein I (beta 2-GPI). Five monoclonal aCL were established from peripheral blood lymphocytes of 3 patients with the APS. The reactivity of monoclonal aCL with various PLs, with DNA, and with beta 2-GPI was examined by enzyme-linked immunosorbent assay (ELISA). All of the monoclonal aCL bound to anionic PLs, only in the presence of beta 2-GPI. Neither monoclonal aCL nor beta 2-GPI bound to DNA. Monoclonal aCL bound to solid-phase beta 2-GPI on polystyrene ELISA plates that had carboxyl groups on their surface, but did not react with solid-phase beta 2-GPI on ordinary polystyrene plates. A mixture of beta 2-GPI and CL inhibited the binding of monoclonal aCL to beta 2-GPI, but CL or beta 2-GPI alone did not. Monoclonal aCL may recognize a cryptic epitope, which appears as a result of beta 2-GPI binding to anionic PLs or to polystyrene with carboxyl groups.


Gallium-68-dotatate PET/CT is better than CT in the management of somatostatin expressing tumors: First experience in Africa.
In this study we aimed to present our experience on the use of Gallium-68-dotatate with positron emission tomography, computed tomography (68 Ga-dotatate PET/CT) in the management of neuroendocrine tumors (NET) and other somatostatin expressing tumors. We retrospectively reviewed patients with histologically confirmed or biochemically suspected NET and other somatostatin expressing (SSTR) tumors imaged at our department with 68Ga-dotatate PET/CT. We determined the performance of this imaging technique as well as its impact on patients management. A total of 203 patients were studied: 103 females, 100 males median age 52years. The commonest tumor type was gastroenteropancreatic NET (41% of patients) and the commonest sites of distant metastases were lymph nodes and the liver 34.0% and 30.5% respectively. Positron emission tomography detected foci of disease in 19 patients where CT was falsely negative. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 68 Ga-dotatate PET/CT imaging of NET and other SST expressing tumors were 94.16%, 91.89%, 95.55%, 89.47% and 96.55% respectively. Gallium-68-dotatate PET/CT was better than CT in detecting primary sites of the disease and highly sensitive and specific for diagnosis and treatment of NET and other SSTR expressing tumors.


Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease.
Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation.


Establishment of the two glioma cell lines: YH and AM.
We have established two human glioma cell lines, which were designated as YH cells and AM cells. The two cell lines have maintained morphological appearance as seen in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture.


[Prevalence of dangerous arrhythmia during pharmacological stress echocardiography].
Pharmacological stress echocardiography (SE) has become a routine diagnostic and prognostic method in patients with ischemic heart disease. However, all stress tests can provoke undesirable adverse effects including dangerous arrhythmia. The aim of the study was to access the prevalence and types of arrhythmia that can appear during SE. A retrospective study included the cohort of patients studied using SE in our Department of Cardiology between 1995 and 2002. We followed the data of 836 patients (pts) (615 men, aged 52 +/- 5 yrs). Dobutamine SE was performed in 695 pts (83.2%) and dipyridamole SE in a group of 141 pts (16.8%). Additionally, atropine was administrated to achieve submaximal heart rate in a group of 694 pts (83%). 519 pts (62%) underwent SE was performed according to high dose protocol and in 317 pts (35%)--low dose protocol. During SE the following arrhythmia events were observed: one persistent ventricular tachycardia (0.12%) and two paroxysmal atrial fibrillation (0.24%) in dobutamine test. The set of unsustained ventricular tachycardia in six patients (0.72%) 5 patients from dobutamine group and 1 from dipyridamole group). Complex forms of ventricular extrasystoles (as bigeminy and trigeminy) in 46 pts (5.5%) 43 in dobutamine SE and 3 in dipyridamole SE. All arrhythmias were mild and withdrew spontaneously or after beta-blockers administration. The risk of dangerous arrhythmia during either dobutamine SE or dipyridamole SE is small and similar in both groups. Dobutamine SE tends to provoke of mild arrhythmia (p = 0.075) more often.


Inhibition of calmodulin-activated smooth-muscle myosin light-chain kinase by calmodulin-binding peptides and fluorescent (phosphodiesterase-activating) calmodulin derivatives.
Aspects of the biochemistry of calmodulin have been addressed that bear on its cell biological role as a mediator of Ca2+ regulation. Calmodulin-binding peptides derived from the amino acid sequence of smooth-muscle myosin light-chain kinase (MLCK) were characterized as inhibitors of calmodulin activation of MLCK-catalyzed phosphorylation of the smooth-muscle regulatory light chain (MLC). MLCK activity was determined by measuring the rate of formation of one of the reaction products, ADP, in a coupled enzymatic assay by continuous fluorimetric monitoring of NADH removal in 100 microM CaCl2 at ionic strength 0.15 M, pH 7.0 and 21 degreesC. The Km value of calmodulin was 3.5 nM, a value 16-35-fold greater than the Kd value of calmodulin for MLCK [Török, K., and Trentham D. R. (1994) Biochemistry 33, 12807-12820]. The different Km and Kd values are most likely associated with the rate-limiting step in MLC phosphorylation being associated with product release from MLCK. The values of the inhibition constants, Ki, were the following: Ac-R-R-K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-CONH2 (Trp peptide), 8.6 (+/-1. 4 sd) pM; Y4-analogue of Trp peptide (Tyr peptide), 7.3 (+/-0.1) nM; and A-R-R-K-W-Q-K-T-G-H-A-V-R-A-I-G-R-L-S-S (RS20-like peptide), 0. 11-0.39 nM. The Ki values were consistent with kinetically determined Kd values of the peptides to calmodulin. Kinetic determination of Kd values required the use of a fluorescently labeled calmodulin, 2-chloro-(epsilon-amino-Lys75)-[6-(4-N, N-diethylamino-phenyl)-1,3,5-triazin-4-yl]-calmodulin (TA-calmodulin).1 Since, as here, Lys75 is a convenient labeling site on calmodulin for the introduction of fluorescent probes, the biological activity of the Lys-modified calmodulins was evaluated. TA-calmodulin and calmodulin selectively modified by 1-N, N-dimethylaminonaphthalene-5-sulfonyl chloride (dansyl-C1) at Lys75 (dansyl-calmodulin) were characterized as activators of cyclic AMP phosphodiesterase (PDE) and inhibitors of MLCK. The Km value for dansyl-calmodulin was equal to that of calmodulin, and that of TA-calmodulin was 3.5-fold greater. TA-calmodulin and Lys75-labeled dansyl-calmodulin thus distinguish between PDE and MLCK being agonists to the former and antagonists to the latter.


Microarray analysis of genes and gene functions in disc degeneration.
The aim of the present study was to screen differentially expressed genes (DEGs) in human degenerative intervertebral discs (IVDs), and to perform functional analysis on these DEGs. The gene expression profile was downloaded from the Gene Expression Omnibus database (GSE34095)and included six human IVD samples: three degenerative and three non-degenerative. The DEGs between the normal and disease samples were identified using R packages. The online software WebGestalt was used to perform the functional analysis of the DEGs, followed by Osprey software to search for interactions between the DEGs. The Database for Annotation, Visualization and Integrated Discovery was utilized to annotate the DEGs in the interaction network and then the DEGs were uploaded to the Connectivity Map database to search for small molecules. In addition, the active binding sites for the hub genes in the network were obtained, based on the Universal Protein database. By comparing the gene expression profiles of the non-degenerative and degenerative IVDs, the DEGs between the samples were identified. The DEGs were significantly associated with transforming growth factor β and the extracellular matrix. Matrix metalloproteinase 2 (MMP2) was identified as the hub gene of the interaction network of DEGs. In addition, MMP2 was found to be upregulated in degenerative IVDs. The screened small molecules and the active binding sites of MMP2 may facilitate the development of methods to inhibit overexpression of MMP2.


Effect of statin therapy on vaspin levels in type 2 diabetic patients.
Statins are commonly used antihyperlipidemic agents, with anti-inflammatory and immunomodulatory properties that are thought to account for a significant portion of their ability to protect against atherosclerosis and cardiovascular disease. Vaspin, a visceral adipose tissue-derived serine protease inhibitor, is an emerging adipokine with important insulin-sensitizing, cardioprotective, and antiatherosclerotic properties in patients with diabetes. In this randomized controlled clinical trial, we evaluated the effect of statin therapy on vaspin levels in patients with type 2 diabetes mellitus. Patients were divided into two groups, ie, those receiving simvastatin (study group, n = 33), and those who did not (control group, n = 29). Patient data, blood biochemistry, and vaspin levels were recorded at the beginning of the study (baseline) and after 8 weeks (end of the study). After 8 weeks of treatment, vaspin levels were increased in patients treated with simvastatin (504.58 ± 203.07 pg/mL at baseline versus 629.15 ± 68.39 pg/mL after 8 weeks, P < 0.01), but not in patients who were not treated with simvastatin (613.33 ± 357.53 pg/mL at baseline versus 582.37 ± 84.63 pg/mL after 8 weeks, P > 0.05). In addition, the lipid-lowering effect of simvastatin was reflected in a statistically significant reduction in total cholesterol in the study group (220.75 ± 55.66 mg/dL at baseline versus 201.90 ± 53.65 mg/dL after 8 weeks P < 0.01) but not in the control group (214.24 ± 47.2 mg/dL at baseline versus 215.72 ± 43.65 mg/dL after 8 weeks, P > 0.05) and in a statistically significant reduction in triglyceride levels in the study group (265.8 ± 210.41 mg/dL at baseline versus 223.03 ± 178.67 mg/dL after 8 weeks, P < 0.05) but not in the control group (225.44 ± 115.13 mg/dL at baseline versus 215.58 ± 110.2 mg/dL after 8 weeks, P > 0.05). Mean vaspin levels were significantly higher in the study group than in the control group. These results indicate that statin therapy increases plasma vaspin levels in addition to having a lipid-lowering effect. This could be a mechanism underlying the pleiotropic effects seen with statins, including their cardioprotective and antiatherosclerotic effects.


[Successful aortic root replacement with pulmonary autograft (Ross) in two cases of congenital aortic stenosis].
Two cases of 7 and 23 year of age with congenital aortic stenosis associated with the small valve annulus underwent successful aortic root replacement with pulmonary autograft (Ross procedure). Preoperative pressure gradient and the valve size were 120 and 80 mmHg, and 16 and 18 mm, respectively. Even with the small native aortic annulus, pulmonary autografts could be implanted to aortic annulus without autograft distortion by the method of total aortic replacement. The right ventricular outflow reconstruction was performed with PTFE-valved bovine pericardial conduit with securing the posterior muscular edge by a strip of autologous aortic wall. Postoperative course in both patients was uneventful without any rhythm disturbances. During the 12 and 14 months of follow-up, both patients were in excellent clinical condition with no evidence of autograft valve regurgitation and functional deterioration of valved conduit. This procedure was thought to be a preferable method of young cases with congenital aortic stenosis.


Locally aggressive orbital giant cell reparative granuloma in an infant: case report and literature review.
Giant cell reparative granuloma (GCRG) is a non-neoplastic hyperplasia of bones that mostly happens in the mandible and maxilla in any age group but has a predilection for children and young adults. GCRGs that cause bone destruction are of very low frequency. Orbital-involved cases have been rarely reported since 1981, especially in children. We now report a 1-year-old girl with a rapidly enlarging post-traumatic orbital mass. CT scan and surgical resection showed a well-defined mass occupying the upper right orbit, causing bone destruction. Microscopically there was a proliferation of histocytes and some osteoclast-like multinucleated giant cells with hemosiderin, finally confirmed to be GCRG. 22 months' follow up showed no evidence of recurrence. This case suggests infant orbital GCRG can be locally aggressive.


Mapping the different methods adopted for diagnostic imaging instruction at medical schools in Brazil.
To map the different methods for diagnostic imaging instruction at medical schools in Brazil. In this cross-sectional study, a questionnaire was sent to each of the coordinators of 178 Brazilian medical schools. The following characteristics were assessed: teaching model; total course hours; infrastructure; numbers of students and professionals involved; themes addressed; diagnostic imaging modalities covered; and education policies related to diagnostic imaging. Of the 178 questionnaires sent, 45 (25.3%) were completed and returned. Of those 45 responses, 17 (37.8%) were from public medical schools, whereas 28 (62.2%) were from private medical schools. Among the 45 medical schools evaluated, the method of diagnostic imaging instruction was modular at 21 (46.7%), classic (independent discipline) at 13 (28.9%), hybrid (classical and modular) at 9 (20.0%), and none of the preceding at 3 (6.7%). Diagnostic imaging is part of the formal curriculum at 36 (80.0%) of the schools, an elective course at 3 (6.7%), and included within another modality at 6 (13.3%). Professors involved in diagnostic imaging teaching are radiologists at 43 (95.5%) of the institutions. The survey showed that medical courses in Brazil tend to offer diagnostic imaging instruction in courses that include other content and at different time points during the course. Radiologists are extensively involved in undergraduate medical education, regardless of the teaching methodology employed at the institution.


Multi-parametric quantitative in vivo spinal cord MRI with unified signal readout and image denoising.
Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed in vivo by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout in vivo (i.e. with matched spatial encoding parameters across a range of imaging contrasts). We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via multi-contrast image denoising methods. As a proof-of-concept, here we provide a demonstration with one such method, known as Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a singular value (SV) decomposition truncation approach that relies on redundant acquisitions, i.e. such that the number of measurements is large compared to the number of components that are maintained in the truncated SV decomposition. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient MP-PCA denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 17% for mean kurtosis, 8% for bound pool fraction (myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from multi-contrast denoising methods such as MP-PCA.


Rheology of hyaluronan solutions under extensional flow.
The extensional viscosity and the steady shear viscosity of sodium type hyaluronan (NaHA) in water with sodium chloride and/or sucrose and in DMSO solvent were measured. The extensional viscosities for HA in aqueous solution (0.05, 0.1, 0.3 w/v%) were constant at lower extensional rates, and then became strain thinning above a critical extensional rate. However, on adding sodium chloride, the extensional viscosity decreased and became strain thickening at higher extensional rates. Sodium ions shield the electrostatic repulsion between carboxyl residues of HA molecules and constrict the coil dimensions. The strain thickening of HA solution in the presence of sodium chloride at higher extension rates is due to the coil stretching. The addition of sucrose increased the extensional viscosity and shifted the critical extensional rate to lower strain rates. With increasing strain (shear) rates, extensional (shear) viscosities for HA aqueous solutions remained constant up to a critical extension (shear) rate; but they showed no plateau and decreased linearly in DMSO. It is clear that molecular interaction of HA in DMSO is stronger than that in aqueous solution. This should be attributed to the different conformations of HA in DMSO and in aqueous solutions.


Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21(low) B cells.
Intravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody deficiencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FcγRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21(low) B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21(low) B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21(low) B cells that undergo accelerated apoptosis.


[Polymorphisms of thymidylate synthase gene and correlation of its protein expression to lymph node metastasis of esophageal squamous cell carcinoma].
Thymidylate synthase (TS) is a key enzyme in DNA synthesis. The 28-bp tandem repeat in the 5'-untranslated region (UTR) of TS gene and the G/C single nucleotide polymorphism (SNP) of TS gene may modify the expression and activity of TS protein, therefore, may change the susceptibility and prognosis of tumors. This study was to explore the correlations of TS 5'-UTR polymorphism to lymph node metastasis of esophageal squamous cell carcinoma (ESCC) and the expression of TS protein. Peripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age-and gender-matched healthy controls. TS 5'-UTR tandem repeat and the G/C SNP genotype was detected by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. TS expression in 51 specimens of ESCC was detected by SP immunohistochemistry. The frequencies of 3G/3G, 3G/3C, 3C/3C, 2R/3G, 2R/3C, 2R/2R, and other genotypes were 17.5%, 17.3%, 29.3%, 12.9%, 17.8%, 3.7%, and 1.5% in the healthy controls, and 16.0%, 16.0%, 29.3%, 13.8%, 17.6%, 4.3%, and 3.0% in the ESCC patients; whereas the frequencies of 3G, 3C, 2R, and other alleles were 32.8%, 47.0%, 19.5%, and 0.7% in the healthy controls, and 31.2%, 46.8%, 20.5%, and 1.5% in the ESCC patients, respectively. Compared with 3G/3G genotype, 2R/3G genotype significantly increased the risk of lymph node metastasis of ESCC [age and gender adjusted odds ratio (OR), 11.53; 95% confidence interval (CI), 2.67-49.74]. TS protein expression was significantly related to TS 5'-UTR genotype (P<0.05), but was not related to gender, age, lymph node metastasis and clinicopathologic stage. TS 5'-UTR tandem repeat and G/C SNP genotype, but not TS expression, might be a candidate molecular marker to predict lymph node metastasis of ESCC.


Stresses and strains on the human fetal skeleton during development.
Mechanical forces generated by fetal kicks and movements result in stimulation of the fetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton in utero have never before been characterized. Here, we quantify the biomechanics of fetal movements during the second half of gestation by modelling fetal movements captured using novel cine-magnetic resonance imaging technology. By tracking these movements, quantifying fetal kick and muscle forces, and applying them to three-dimensional geometries of the fetal skeleton, we test the hypothesis that stress and strain change over ontogeny. We find that fetal kick force increases significantly from 20 to 30 weeks' gestation, before decreasing towards term. However, stress and strain in the fetal skeleton rises significantly over the latter half of gestation. This increasing trend with gestational age is important because changes in fetal movement patterns in late pregnancy have been linked to poor fetal outcomes and musculoskeletal malformations. This research represents the first quantification of kick force and mechanical stress and strain due to fetal movements in the human skeleton in utero, thus advancing our understanding of the biomechanical environment of the uterus. Further, by revealing a potential link between fetal biomechanics and skeletal malformations, our work will stimulate future research in tissue engineering and mechanobiology.


Public health considerations for the use of a first generation HIV vaccine. Report from a WHO-UNAIDS-CDC consultation, Geneva, 20-21 November 2002.
To accelerate the development and future availability of safe, effective and affordable HIV vaccines it is essential to address not only the associated biomedical obstacles, but also the logistic aspects that would guide the introduction and use of those vaccines. It is likely that initial vaccines may only be partially effective, and their public health use will have to be carefully considered. This report summarizes the discussions from a consultation held in Geneva (20-21 November 2002) organized by the World Health Organization (WHO), the joint United Nations Programme on HIV/AIDS (UNAIDS) and the US Centers for Disease Control and Prevention (CDC). The group identified a number of logistic issues that need to be addressed to accelerate the development and future availability of HIV vaccines, and made broad recommendations in four different areas: (a) Vaccine manufacturing and licensing; (b) vaccination acceptability and social marketing; (c) immunisation strategies and delivery; and (d) access and economic issues. The implementation of these recommendations will require the participation of multiple stakeholders in the public and private sector, in industrialized and developing countries. These actions will be essential to ensure widespread and rapid access to HIV vaccines globally, soon after their efficacy is demonstrated in clinical trials.


Crestal bone remodeling around implants placed using a short drilling protocol.
The aim of the study was to examine the influence of a short drilling protocol on peri-implant crestal bone levels. Forty implants were placed in the posterior mandibles of 20 patients. The implants (diameter, 4.2 mm; length, 10 to 11.5 mm) were inserted in pairs: one implant was inserted using the standard drilling protocol (five drills in sequence), while the other was inserted using the short drilling protocol sequence (three drills). All implants received healing abutments and were restored with single-unit restorations after 3 months of healing. Analysis of crestal bone level was based on radiographs taken at insertion and at 3, 6, and 12 months after insertion. The results were analyzed using software Image J 1.46r (National Institutes of Health). Crestal bone level was measured in millimeters at the distal aspect of each implant. None of the implants in either group was lost during the 12-month follow-up period, and all patients completed the follow-up examination. The drilling time for the insertion of one implant with the short drilling protocol was 1.03 ± 3.63 minutes compared to 1.57 ± 2.88 minutes for the standard protocol. The mean values of crestal bone loss at 12 months were 0.94 ± 0.43 mm for implants placed using the standard protocol and 0.90 ± 0.33 mm for implants placed using the short drilling protocol. No statistically significant differences were noted. Using the short drilling protocol reduced the surgery time by approximately 50% and did not affect crestal bone remodeling during the first year postinsertion.


Spatial and temporal epidemiology of malaria in extra-Amazonian regions of Brazil.
Mosquitoes, Plasmodium parasites, and humans live in sympatry in some extra-Amazonian regions of Brazil. Recent migrations of people from Amazonia and other countries to extra-Amazonian regions have led to many malaria outbreaks. Lack of relevant expertise among health professionals in non-endemic areas can lead to a neglect of the disease, which can be dangerous given its high fatality rate. Therefore, understanding the spatial and temporal epidemiology of malaria is essential for developing strategies for disease control and elimination. This study aimed to characterize imported (IMP) and autochthonous/introduced (AU/IN) cases in the extra-Amazonian regions and identify risk areas and groups. Epidemiological data collected between 2007 and 2014 were obtained from the Notifiable Diseases Information System of the Ministry of Health (SINAN) and from the Department of the Unified Health System (DATASUS). High malaria risk areas were determined using the Local Indicator of Spatial Association. IMP and AU/IN malaria incidence rates were corrected by Local Empirical Bayesian rates. A total of 6092 malaria cases (IMP: 5416, 88.9 %; AU/IN: 676, 11.1 %) was recorded in the extra-Amazonian regions in 2007-2014. The highest numbers of IMP and AU/IN cases were registered in 2007 (n = 862) and 2010 (n = 149), respectively. IMP cases were more frequent than AU/IN cases in all states except for Espírito Santo. Piauí, Espírito Santo, and Paraná states had high incidences of AU/IN malaria. The majority of infections were by Plasmodium falciparum in northeast and southeast regions, while Plasmodium vivax was the predominant species in the south and mid-west showed cases of dual infection. AU/IN malaria cases were concentrated in the coastal region of Brazil, which contains the Atlantic Forest and hosts the Anopheles transmitters. Several malaria clusters were also associated with the Brazilian Pantanal biome and regions bordering the Amazonian biome. Malaria is widespread outside the Amazonian region of Brazil, including in more urbanized and industrialized states. This fact is concerning because these highly populated areas retain favourable conditions for spreading of the parasites and vectors. Control measures for both IMP and AU/IN malaria are essential in these high-risk areas.


The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure.
In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th-75th percentile 1897-6486] versus 1788 [682-3870], adjusted p < 0.001, versus 2231 pg/mL [902-5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062-5253] versus 2545 [1686-4337], adjusted p = 0.36, versus 2294 [1471-3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF.


Spontaneous remission of the micronodular pattern in cryptogenic organizing pneumonia.
Organizing pneumonia (OP) is a common interstitial lung disease, pathologically characterized by polypoid granulation tissue in the alveolar ducts and alveoli. In clinical practice, OP occasionally presents as non-resolving pneumonia. The typical radiographic pattern of OP is characterized by dense consolidation with ground-glass opacities. Diffuse micronodular pattern of OP (MNOP) is a rare radiographic manifestation that mimics non-resolving bronchiolar diseases such as pulmonary tuberculosis or hypersensitivity pneumonitis. Steroid therapy is usually effective for MNOP; however, spontaneous remission in MNOP has never been reported. Herein, we report a case of a diffuse micronodular form of cryptogenic OP (COP) that was diagnosed via transbronchial biopsy (TBB) and resolved spontaneously within a few months. Our case highlights that MNOP may resolve spontaneously similar to other forms of OP, and mild cases may be under-recognized. Furthermore, careful observation could be an option for managing MNOP with mild and non-progressive symptoms.


Interplay between demixing and freezing in two-dimensional symmetrical mixtures.
The interplay between demixing and freezing in two-dimensional symmetrical binary mixtures of Lennard-Jones particles is studied using Monte Carlo simulation. It is demonstrated that different scenarios are possible. For example, the line of continuous liquid demixing transition can start at the liquid side of the vapor-liquid coexistence at the lower critical end point and then it can terminate at the liquid side of the liquid-demixed solid coexistence at the upper critical end point. Other situations are also possible. We distinguish four different scenarios depending on the interactions between unlike particles.


Polycystic kidney and liver disease in two related West Highland White Terrier litters.
Polycystic kidney and liver disease was present in four of six female and three of five male offspring born in two matings between the same pair of West Highland White Terriers. Clinical signs were apparent and serum biochemistry analysis consistent with liver failure was evident by 5 weeks of age. Affected pups were euthanatized because of their disease. Renal cysts were confirmed to be of collecting duct origin by Dolichos bifluros agglutinin lectin histochemistry, and hepatic cysts were of biliary origin. The clinically unaffected parents were related through multiple common ancestors, and there were no reports of similar disease in related dogs. An autosomal recessive mode of inheritance is therefore suggested. This is the first report of polycystic kidney and liver disease in the West Highland White Terrier. The features of the disease in these pups are similar to those of autosomal recessive polycystic kidney disease (ARPKD) in humans. The West Highland White Terrier may therefore be a potential animal model for ARPKD.


Adhesion and colonisation of Candida krusei on host surfaces.
Candida krusei is an emerging pathogen, especially in immunocompromised hosts. As the adherence of this organism both to host epithelial surfaces and to catheter and prosthetic surfaces appears to be important in the pathogenesis of superficial as well as systemic candidoses, the adhesion of 20 oral isolates of C. krusei and five oral isolates of C. albicans was compared with the following substrates: cultured (HeLa) epithelial cells, buccal epithelial cells (BEC) from healthy adults and bone marrow transplant patients, and acrylic (polymethylmethacrylate) surfaces. Animal experiments in Sprague Dawley rats were also conducted to evaluate the relative oral carriage rate of the two Candida spp. C. krusei isolates adhered in far greater numbers to acrylic surfaces than to either of the cell surfaces. Significant intra-species differences in C. krusei adhesion for acrylic surfaces were noted between 74 (39%) of 190 pair comparisons in contrast to 18 (9.5%) of 190 with HeLa surfaces (p < 0.05). A positive correlation was also observed between the adhesion of C. krusei isolates to HeLa cells and acrylic surfaces. Five isolates of C. albicans showed very low adherence to HeLa surfaces when compared with BEC obtained from either healthy individuals or bone marrow transplant patients. The adherence of C. albicans to BEC from the healthy individuals was c. 12-fold greater than that of C. krusei, a figure similar to the relative murine oral carriage rate of the two Candida spp.(ABSTRACT TRUNCATED AT 250 WORDS)


Base-promoted synthesis of dihydrochromeno[4,3-d]pyrrolo[3,4-b]pyridines from 4-chloro-3-substituted coumarins and α-aminomaleimides.
This paper describes the base-mediated cascade reactions of 4-chloro-3-substituted coumarins with α-aminomaleimides, allowing the efficient synthesis of dihydrochromeno[4,3-d]pyrrolo[3,4-b]pyridines with interesting chemoselectivity. These transformations include the domino-style formation of C-C/C-N bonds through a base-mediated nucleophilic substitution, Michael addition, N-cyclization, and elimination. The presented synthetic strategy has several advantages: it is simple, uses readily available starting materials and an environmentally friendly solvent, has a highly chemoselective route, and allows the purification of products via washing with EtOH (96%), a technique called GAP (Group-Assisted-Purification) chemistry.


Elimination of circulating antibodies. Attempts to eliminate antibodies circulating in rabbits using a fraction of normal human epidermis.
Rabbits were immunised with a fraction of normal human epidermis to produce circulating antibodies. In each experiment, half of the immunised rabbits were given a dose of the same antigen intravenously and the changes in the titres of antibodies were recorded. Doses of the antigen used in different experiments varied from 0.09 to 3.5 mg protein per rabor the first 24 h, followed by a secondary rise. Administration of corticosteroids together with the antigen intravenously could check this secondary rise in antibody titre. Repeated intravenous injections of the antigen led to severe anaphylactic reactions, while subcutaneously administered antigen produced no significant effects.


Multisensory Stimulation Reverses Memory Impairment in Adrβ3KO Male Mice.
Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrβ: β1, β2 and β3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrβ3 (Adrβ3KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrβ3KO mice were exposed to an 8-week multisensory stimulation (MS) protocol that comprised gustatory and olfactory stimuli of positive and negative valence; intellectual challenges to reach food; the use of hidden objects; and the presentation of food in ways that prompted foraging, which was followed by analysis of GFAP, Iba-1 and EAAT2 protein expression in the hippocampus (HC) and amygdala (AMY). The MS protocol reduced GFAP and Iba-1 expression in the HC of young mice but not in older mice. While this protocol restored memory impairment when applied to Adrβ3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrβ3KO mice. In the AMY of Adrβ3KO older mice, we observed an increase in GFAP and EAAT2 expression when compared to wild-type (WT) mice that MS was unable to reduce. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied immediately after weaning in Adrβ3KO animals and indicates that the control of neuroinflammation mediates this response.


[The concept of missed care: a literature review].
To describe the concept and consequences of missed nursing care. A literature review was conducted searching on Medline, Trip Database, Cinahl, Cochrane, with the following key words: missed care, missed nursing care. Any needed nursing intervention omitted (totally or in part) or postponed is considered missed care. The causes of missed care are the scarcity of human resources, of equipment or communication, but also the criteria for setting priorities and the relationships with nurses aids may also have an impact. The missed care may be measured with the Misscare tool: those more frequently missed are deambulation, passive mobilization, hygiene and oral care. CONCLUSIONS. A description of the interventions omitted or only postponed at international level, a measurement of the variability of missed care according to the number of nurses, and their impact on patients'outcomed could improve a better understanding of this problem.


Frequency and direction of competitive anger in contact sports.
The purpose of the present study was to investigate whether athletes involved in physical contact sports may interpret their feelings of anger as facilitative of performance, and to examine differences in the interpretation of anger as a function of the type of sport (team vs individual) or the competitive skill level (high vs low). A modified version of the State-Trait Anger Expression Inventory was administered to 100 Italian adult male athletes practicing rugby or individual combat sports (judo, freestyle wrestling, or Greco-Roman wrestling). The questionnaire was intended to measure the frequency and the direction (i.e., the facilitative-debilitative interpretation) of competitive anger. Many athletes engaged in contact sports tended interpret their competitive anger as facilitative of performance rather than debilitative. The type of sport and the athlete's standard level can mediate the individual's interpretation of the effects of anger symptoms upon performance. Competitors can interpret their anger as helpful to energize behavior and channel physical and mental resources for skill execution. Practitioners should assist athletes in gaining control over anger rather than attempting to suppress it.


Case-control study of screening for prostatic cancer by digital rectal examinations.
Although commonly thought to be an effective method of screening for prostatic cancer, digital rectal examinations have yet to be shown by controlled study to help prevent advanced forms of this disease. 139 men with metastatic (stage D) prostatic cancer (cases) were compared with an equal number of matched men free of this condition (controls), with respect to rectal examinations recorded in the medical records up to, on average, 23 years before the cases' initial diagnosis of prostatic cancer. Cases and controls were members of a large health maintenance organisation in northern California. In the 10 years before initial diagnosis (excluding the last three months) the average number of examinations for routine screening (2.45 vs 2.52) or to evaluate intestinal or rectal symptoms (0.44 in both) were similar in cases and controls, respectively. After adjustment for racial differences, the relative risk of metastatic prostatic cancer for men with one or more screening rectal examinations compared with men with none was 0.9 with a 95% confidence interval of 0.5-1.7. Screening by routine digital rectal examination appears to have little if any effect in preventing metastatic prostatic cancer. If there is a small benefit, it will be difficult to demonstrate by conventional epidemiological study.


Sn-induced low-temperature growth of Ge nanowire electrodes with a large lithium storage capacity.
We herein present the synthesis of germanium (Ge) nanowires on Au-catalyzed low-temperature substrates using a simple thermal Ge/Sn co-evaporation method. Incorporation of a low-melting point metal (Sn) enables the efficient delivery of Ge vapor to the substrate, even at a source temperature below 600 °C. The as-synthesized nanowires were found to be a core/shell heterostructure, exhibiting a uniform single crystalline Ge sheathed within a thin amorphous germanium suboxide (GeO(x)) layer. Furthermore, these high-density Ge nanowires grown directly on metal current collectors can offer good electrical connection and easy strain relaxation due to huge volume expansion during Li ion insertion/extraction. Therefore, the self-supported Ge nanowire electrodes provided excellent large capacity with little fading upon cycling (a capacity of ∼900 mA h g(-1) at 1C rate).


[Hepatocyte growth factor recruits endothelial progenitor cells from bone marrow into blood circulation].
To assess whether hepatocyte growth factor recruits bone marrow-derived endothelial progenitor cells into blood circulation to participate in postnatal angiogenesis and endothelium repair. The adenovirus vector encoding HGF gene (Ad-HGF) were intravenous administrated into BALB/c mice, and then serum HGF was determined by enzyme-linked immunosorbent assay, the number of CD34+ cells in peripheral blood was assayed by flow cytometry, and the nucleated cells in peripheral blood were isolated, cultured and the endothelial cell colonies were characterized by staining with antibodies against tie-2, vWF. The carbon tetrachloride-induced liver damage model of female mice was established. The peripheral blood nucleated cells of Ad-HGF treated male mice were intravenous administrated into these mice, and 4 weeks later, in situ hybridization for the sry gene was used to identify the implanted cells in the damaged tissues. Intravenous administration of Ad-HGF resulted in significant elevation of serum hepatocyte growth factor level and induced profoundly increase of endothelial progenitor cells in the peripheral blood, which were characterized by their ability to form endothelial cell colonies in culture and expression of CD34, tie-2, and vW factor. HGF-mobilized endothelial progenitors could incorporate into sites of neovascularization in a liver regeneration model. Hepatocyte growth factor could markedly recruit bone marrow-derived endothelial progenitor cells into blood circulation.


Finding optimal photosensitisers for the decontamination of foods by the photodynamic effect.
A new method for sanitation based on the photodynamic effect is introduced. Photosensitisers are compounds that generate cytotoxic oxygen species and free radicals after excitation with appropriate visible light. The cell killing efficacy is due to their chemical structure, to the actual environment and therefore also to their degree of aggregation. As has been shown, photosensitisers bound to the cell wall or incorporated into the cells are very effective cytotoxic agents after illumination. Even singlet oxygen generated in the gas phase surrounding the micro-organisms effectively kills cells. Especially membrane components are the targets of the photodynamic effect. Membrane disintegration is observed soon after illumination. The food contaminants under investigation are Bacillus subtilis, Bacillus cereus, forming endospores, Staphylococcus aureus, forming a wide range of agressins, exotoxins and enterotoxins, all gram positive micro-organisms, Escherichia coli, a hygiene indicator, and the yeasts Saccharomyces cerevisiae, Kloeckera javanica, Rhodotorula mucilaginosa, a blue and a pink pigmented isolate from foods. We investigated the capacity of several photosensitisers to induce the phototoxic effect towards those micro-organisms following excitation by visible light.


Species-specific escape of Plasmodium sporozoites from oocysts of avian, rodent, and human malarial parasites.
Malaria is transmitted when an infected mosquito delivers Plasmodium sporozoites into a vertebrate host. There are many species of Plasmodium and, in general, the infection is host-specific. For example, Plasmodium gallinaceum is an avian parasite, while Plasmodium berghei infects mice. These two parasites have been extensively used as experimental models of malaria transmission. Plasmodium falciparum and Plasmodium vivax are the most important agents of human malaria, a life-threatening disease of global importance. To complete their life cycle, Plasmodium parasites must traverse the mosquito midgut and form an oocyst that will divide continuously. Mature oocysts release thousands of sporozoites into the mosquito haemolymph that must reach the salivary gland to infect a new vertebrate host. The current understanding of the biology of oocyst formation and sporozoite release is mostly based on experimental infections with P. berghei, and the conclusions are generalized to other Plasmodium species that infect humans without further morphological analyses. Here, it is described the microanatomy of sporozoite escape from oocysts of four Plasmodium species: the two laboratory models, P. gallinaceum and P. berghei, and the two main species that cause malaria in humans, P. vivax and P. falciparum. It was found that sporozoites have species-specific mechanisms of escape from the oocyst. The two model species of Plasmodium had a common mechanism, in which the oocyst wall breaks down before sporozoites emerge. In contrast, P. vivax and P. falciparum sporozoites show a dynamic escape mechanism from the oocyst via polarized propulsion. This study demonstrated that Plasmodium species do not share a common mechanism of sporozoite escape, as previously thought, but show complex and species-specific mechanisms. In addition, the knowledge of this phenomenon in human Plasmodium can facilitate transmission-blocking studies and not those ones only based on the murine and avian models.


Crop rotation and inoculation increase soil bradyrhizobia population, soybean grain yields, and profitability.
Crop rotation and rhizobial inoculation are strategies to increase yield by means of organic matter addition and modulation of microbial diversity. However, the extent to which these agricultural practices change soil Bradyrhizobium populations, soybean grain yield, and economic benefits to farmers is unclear. Thus, this study aimed to evaluate the interaction between crop rotation and inoculation of soybean (Glycine max) cultivated in two contrasting soils (clayey and sandy soil) on biological nitrogen fixation components, grain yields, and profits. Field experiments with a three-year crop rotation system were carried out to compare effects of inoculation and crop rotations on soil chemical attributes, bradyrhizobia most probable number (MPN) and diversity, soybean nodulation, grain yield, and economic indicators of inoculation in different crop rotations. The crop rotation did not affect the soil MPN cells of bradyrhizobia, but the inoculation and the soil sampling time did, ranging from 3.61-4.42 to 4.40-4.82 in the sandy soil, while in the clayey soil they were from 5.19-6.34 to 6.61-7.14 in Log10 per g of soil with higher population after harvest of summer crops. In the clayey soil, crop rotation influenced soybean nodulation. The grain yield of inoculated soybean in the clayey soil was higher than that in the sandy soil. Soybean inoculation with Bradyrhizobium spp. increased the profitability of agricultural production systems by up to 45% in clayey soil and up to 7% in sandy soil.


Imaging techniques as predictive and prognostic biomarkers in renal cell carcinoma.
A number of imaging modalities are showing promise as predictive and prognostic biomarkers in advanced renal cell carcinoma. This review discusses progress to date in this exciting area and identifies areas of future promise.


Effect of Mg-Modified Waste Straw Biochar on the Chemical and Biological Properties of Acidic Soils.
Biochar is important for soil improvement, fertilizer innovation, and greenhouse gas reduction. In this paper, Mg-modified biochar was prepared from rice and corn straw and mixed with soil at a 1% (w/w) addition in an indoor soil simulation experiment to study the effect of Mg-modified biochar on the chemical properties of acidic soil. The results showed that the addition of Mg-modified biochar reduced soil acidity and improved soil fertility. Compared with the control group, the Mg-modified biochar treatment significantly increased the concentrations of available potassium, available phosphorus, total phosphorus, organic carbon and exchangeable calcium and magnesium in the soil, and effectively increased the concentration of total nitrogen. Rice straw Mg-modified biochar treatment was more effective in increasing the soil-available potassium, available phosphorus, total phosphorus and exchangeable magnesium concentration, while corn straw Mg-modified biochar was more effective in increasing the soil organic carbon and exchangeable calcium concentration. In addition, the high pyrolysis temperature of Mg-modified biochar was more effective in promoting the soil-available potassium, available phosphorus and total nitrogen concentration, while the low pyrolysis temperature of Mg-modified biochar was more effective in promoting soil alkaline nitrogen, exchangeable calcium and magnesium.


Virtual daily living test to screen for mild cognitive impairment using kinematic movement analysis.
Questionnaires or computer-based tests for assessing activities of daily living are well-known approaches to screen for mild cognitive impairment (MCI). However, questionnaires are subjective and computerized tests only collect simple performance data with conventional input devices such as a mouse and keyboard. This study explored the validity and discriminative power of a virtual daily living test as a new diagnostic approach to assess MCI. Twenty-two healthy controls and 20 patients with MCI were recruited. The virtual daily living test presents two complex daily living tasks in an immersive virtual reality environment. The tasks were conducted based on subject body movements and detailed behavioral data (i.e., kinematic measures) were collected. Performance in both the proposed virtual daily living test and conventional neuropsychological tests for patients with MCI was compared to healthy controls. Kinematic measures considered in this study, such as body movement trajectory, time to completion, and speed, classified patients with MCI from healthy controls, F(8, 33) = 5.648, p < 0.001, η2 = 0.578. When both hand and head speed were employed in conjunction with the immediate free-recall test, a conventional neuropsychological test, the discrimination power for screening MCI was significantly improved to 90% sensitivity and 95.5% specificity (cf. the immediate free-recall test alone has 80% sensitivity and 77.3% specificity). Inclusion of the kinematic measures in screening for MCI significantly improved the classification of patients with MCI compared to the healthy control group, Wilks' Lambda = 0.451, p < 0.001.


Assessment of left atrial appendage wall velocities by transesophageal tissue Doppler echocardiography: a clinical study in patients with sinus rhythm.
To assess left atrial appendage (LAA) wall velocities, 42 patients in sinus rhythm underwent tissue Doppler interrogation during a clinically indicated transesophageal echocardiography. Color Doppler (B-mode and M-mode) and pulsed Doppler of LAA walls were obtained and analyzed in all patients. Color-coded tissue Doppler rendered a qualitative assessment of LAA wall, depicting both the timing and the sequence of LAA contraction. With pulsed Doppler interrogation, a triphasic signal was recorded in all patients, consisting of a positive wave (D1), followed by a biphasic wave (positive D2 and negative D3). Peak velocities of D1, D2, and D3 were 6.1 +/- 2, 20.1 +/- 7, and 16.1 +/- 5 cm/s, respectively. Mean coefficient of variation of LAA wall velocities was 6%, significantly lower than that of LAA percentage area change (29%). Compared with patients with abnormal relaxation, patients with normal mitral inflow had higher D1 peak velocities (7.3 +/- 1.2 vs 4.3 +/- 1 cm/s, respectively; P <.0001). Time sequence of ECG, LAA flow, and mitral inflow indicates that D1 component of LAA wall occurs in early diastole and is likely due to the upward movement of the mitral ring toward the base of the LAA wall. In conclusion, evaluation of LAA wall using tissue Doppler is feasible and reproducible. Although color tissue Doppler analysis allows a qualitative assessment, pulsed Doppler gives new quantitative insights for the comprehensive assessment of LAA wall dynamics, which complements the information obtained with flow interrogation.


Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.
Up to 30% of acute stroke evaluations are deemed stroke mimics, and these are common in telestroke as well. We recently published a risk prediction score for use during telestroke encounters to differentiate stroke mimics from ischemic cerebrovascular disease derived and validated in the Partners TeleStroke Network. Using data from 3 distinct US and European telestroke networks, we sought to externally validate the TeleStroke Mimic (TM) score in a broader population. We evaluated the TM score in 1930 telestroke consults from the University of Utah, Georgia Regents University, and the German TeleMedical Project for Integrative Stroke Care Network. We report the area under the curve in receiver-operating characteristic curve analysis with 95% confidence interval for our previously derived TM score in which lower TM scores correspond with a higher likelihood of being a stroke mimic. Based on final diagnosis at the end of the telestroke consultation, there were 630 of 1930 (32.6%) stroke mimics in the external validation cohort. All 6 variables included in the score were significantly different between patients with ischemic cerebrovascular disease versus stroke mimics. The TM score performed well (area under curve, 0.72; 95% confidence interval, 0.70-0.73; P<0.001), similar to our prior external validation in the Partners National Telestroke Network. The TM score's ability to predict the presence of a stroke mimic during telestroke consultation in these diverse cohorts was similar to its performance in our original cohort. Predictive decision-support tools like the TM score may help highlight key clinical differences between mimics and patients with stroke during complex, time-critical telestroke evaluations.


Effects of diluents on cell culture viability measured by automated cell counter.
Commercially available automated cell counters based on trypan blue dye-exclusion are widely used in industrial cell culture process development and manufacturing to increase throughput and eliminate inherent variability in subjective interpretation associated with manual hemocytometers. When using these cell counters, sample dilution is often necessary to stay within the assay measurement range; however, the effect of time and diluents on cell culture is not well understood. This report presents the adverse effect of phosphate buffered saline as a diluent on cell viability when used in combination with an automated cell counter. The reduced cell viability was attributed to shear stress introduced by the automated cell counter. Furthermore, length of time samples were incubated in phosphate buffered saline also contributed to the observed drop in cell viability. Finally, as erroneous viability measurements can severely impact process decisions and product quality, this report identifies several alternative diluents that can maintain cell culture viability over time in order to ensure accurate representation of cell culture conditions.


Understanding cutaneous tuberculosis: two clinical cases.
Tuberculosis (TB) is an ancient human disease and remains today one of the most important public health problems and the second most frequent cause of death from an infectious disease worldwide. While pulmonary TB is the most common form, extra-pulmonary TB is on the rise due to the increase in immunosuppressed subjects. Cutaneous TB manifestations are rare forms of extra-pulmonary TB due to systemic dissemination of bacilli or direct inoculation, involving skin or skin-associated tissue, more common in immunocompromised subjects. Some risk factors and the features of the lesion may prompt the suspicion of cutaneous TB, but only microbiological assays can confirm the diagnosis. Our work summarizes cutaneous TB manifestations and differences from other skin mycobacterial infections, also describes two characteristic clinical cases.


Syntactic and conceptual factors in children's understanding of metaphors.
A multiple-choice listening task was designed in which 7- and 9-year-old children (n = 30 per group) were presented with nine instances of four different types of metaphoric sentences: perceptual-predicative, psychological-predicative, perceptual-proportional, and psychological-proportional. When factors of memory and attention, sentence length, semantics, and novelty were controlled for, proportional metaphors proved to be significantly more difficult than predicative, but perceptual did not differ from psychological in ease of understanding. No interactions were significant. Nine-year-olds demonstrated metaphoric understanding superior to that of 7-year-olds, despite the fact that children of both ages were familiar with the underlying semantic features of the metaphors and understood all key words at a literal level. Implications for future research are discussed.


Efficient recognition of facial expressions does not require motor simulation.
What mechanisms underlie facial expression recognition? A popular hypothesis holds that efficient facial expression recognition cannot be achieved by visual analysis alone but additionally requires a mechanism of motor simulation - an unconscious, covert imitation of the observed facial postures and movements. Here, we first discuss why this hypothesis does not necessarily follow from extant empirical evidence. Next, we report experimental evidence against the central premise of this view: we demonstrate that individuals can achieve normotypical efficient facial expression recognition despite a congenital absence of relevant facial motor representations and, therefore, unaided by motor simulation. This underscores the need to reconsider the role of motor simulation in facial expression recognition.


High Position of the Third Renal Transplant and Alternative Urinary Tract Reconstruction in a Complicated Case.
The decision-making process for treatment of patients with end-stage renal failure, multiple failed renal transplants, and severe comorbidities can be exceedingly difficult due to the inapplicability of many common surgery methods. In this article, we report the treatment of such a patient who underwent a third renal transplant and subsequently developed a ureteral stenosis. The third kidney had been transplanted with a high abdominal position and a partially intra- and retroperitoneally placed ureter due to a bilaterally obtained iliac fossa and severe abdominal adhesions. For the severe ureteric stenosis, an alternative urinary tract reconstruction was developed by making use of the native ureter contralateral to the graft by tunneling under the sigmoid. We recommend this surgical method as a valid alternative for patients with severe ureteric graft stenosis, when treatment with stenting and common surgical ureter reconstruction methods are not feasible.


Representational momentum in spatial hearing.
The final position of a moving visual object usually appears to be displaced in the direction of motion. We investigated this phenomenon, termed representational momentum, in the auditory modality. In a dark anechoic environment, an acoustic target (continuous noise or noise pulses) moved from left to right or from right to left along the frontal horizontal plane. Listeners judged the final position of the target using a hand pointer. Target velocity was 8 degrees s(-1) or 16 degrees s(-1). Generally, the final target positions were localised as displaced in the direction of motion. With presentation of continuous noise, target velocity had a strong influence on mean displacement: displacements were stronger with lower velocity. No influence of sound velocity on displacement was found with motion of pulsed noise. Although these findings suggest that the underlying mechanisms may be different in the auditory and visual modality, the occurrence of displacements indicates that representational-momentum-like effects are not restricted to the visual modality, but may reflect a general phenomenon with judgments of dynamic events.


c-Met and miRs in Cancer.
c-Met, a member of the receptor tyrosine kinase family, is involved in a wide range of cellular processes, including tumor survival, cell growth, angiogenesis and metastasis, and resulting in overexpression in many human cancers, leading to a constitutive activation of the downstream pathways. Recently identified MicroRNAs are a family of small noncoding RNA molecules, extensively studied in cancer, that exert their action by inhibiting gene expression at the posttranscriptional level in several biological processes. Aberrant regulation of microRNAs expression has been implicated in the pathogenesis of different human neoplasia. Several publications point out the connections between c-Met and its ligand hepatocyte growth factor (HGF) and microRNAs. This review summarizes the current knowledge about the interplay between c-Met/HGF and microRNAs and provides evidence that microRNAs are a novel and additional system to regulate c-Met expression in tumors. In the future, microRNAs connected to c-Met may provide an additional option to inhibiting this oncogene from orchestrating an invasive growth program.


Neurophysiological alterations in caudate neurons in aged cats.
These neurophysiological studies provide information on the alterations in functional capacity of neurons in the aging caudate nucleus (Cd) of the cat. The major finding is that there is a marked loss of excitation in the Cd during the aging process. This loss is most apparent in animals 11-14 years of age but is demonstrable in animals 6-7 years of age. Extracellular recording techniques were used to test the ability of Cd neurons to respond to activation of two of their major inputs, the precruciate cortex (CX) and the substantia nigra (SN). Types of responses that were evoked in both 1-3- and 11-14-year groups were similar and consisted of excitation, excitation followed by inhibition of action potentials or inhibition alone without preceding excitation. The frequency of occurrence of these responses was altered in the aged animals when either input was stimulated. In 1-3-year-old cats CX stimulation evoked initially excitatory responses in 75% of the cells tested while in 11-14-year-old cats excitatory responses occurred in 62% of the cells. When the SN was stimulated the decrease in initial excitation was greater (69% in 1-3- vs 35% in 11-14-year groups). In all aged animals but not in 1-3-year-old cats stimulation thresholds were higher (39-79%) for evoking excitatory responses than for evoking inhibitory responses. In order to assess synaptic security, the ability of Cd neurons to respond to iterative stimulation was determined. Distributions of the minimum interval necessary to evoke two excitatory responses were constructed. There was a marked increase in the proportion of longer intervals in the aged animals indicating that the synaptic response was less secure. There was a tendency for more of the responses in aged animals to have shorter latencies. This result was probably due to loss of less secure longer latency responses that are mediated via multisynaptic pathways. These findings indicate that there are functional changes in a population of Cd neurons in aged cats that impair their ability to process information.


Bronchoscopic intervention as a main treatment for tracheobronchial adenoid cystic carcinoma.
Bronchial adenoid cystic carcinoma (ACC) is a rare disease with low malignancy and indolent progression. Airway obstruction caused by ACC can be resolved by endoscopic procedures. The efficacy of different techniques of bronchoscopic interventions for ACC has not been determined. From November 2004 to March 2012, ACC patients, mainly treated with different techniques of bronchoscopic interventions in our hospital, were reviewed. The study included 37 ACC patients. Five patients (13.5%) with intra-luminal type underwent bronchoscopic therapies for a median of three times (range 1-6 times). Thirty-two patients (86.5%) with mixed type underwent bronchoscopic interventions for a median of 14 times (range 4-20 times). The dyspnea index was significantly improved after the first endoscopic procedure. The overall five- and ten-year survival rate was 85.9% and 45.9%, respectively, similar to surgery-dominant treatments. The present study demonstrates that different procedures of bronchoscopic interventions, as main treatments for ACC, are as effective as surgery-dominant treatment. More prospective and multicentric studies are required to confirm these favorable results, which may influence the therapeutic strategy for ACC in the future.


Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment.
Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.


The prevalence of antibodies to an Epstein-Barr virus-induced polypeptide (EBNA-2) in the sera of rheumatoid arthritic families.
Using the protein immunoblot technique, antibodies to an Epstein-Barr virus-induced 92 kD polypeptide (EBNA-2) were more frequently present in the sera of patients with rheumatoid arthritis and their consanguineous relatives when compared with a control group. No association of anti-EBNA-2 antibody with the HLA-DR antigens was observed.


Adolescent females who have sexually offended: comparisons with delinquent adolescent female offenders and adolescent males who sexually offend.
Very little is known about adolescent females who commit sexual offenses. In this two-part exploratory study, a sample of 11 adolescent females with sexual offense histories is described. In Study I, the sample is compared to an age-matched sample of 11 adolescent females with non-sexual victim-involved offense histories. The sexually offending group had significantly fewer antisocial behavior problems, such as alcohol or drug use problems, problems with fighting, or problems at school. They began their offense behaviors at younger ages than their non-sex offending delinquent peers. Few differences emerged with respect to attitudes about offense behaviors, such as level of denial. In Study II, the same sample of females with sex offense histories was compared with a group of age-matched adolescent males with sex offense histories. The two sex-offending groups were found to be remarkably similar. There were few differences with respect to psychosocial and criminal histories, antisocial behavior, and variables related to clinical presentation and treatment (e.g., level of denial about offense). Likewise, the two groups are remarkably similar with respect to specific sex offense behaviors. The females, however, appear to have experienced more severe and pervasive abuse compared to the males.