The costs of locomotor activity? Maximum body temperatures and the use of torpor during the active season in edible dormice.
Measuring T b during the active season can provide information about the timing of reproduction and the use of short bouts of torpor and may be used as a proxy for the locomotor activity of animals (i.e., maximum T b). This kind of information is especially important to understand life-history strategies and energetic costs and demands in hibernating mammals. We investigated T b throughout the active season in edible dormice (Glis glis), since they (i) have an expensive arboreal life-style, (ii) are known to show short bouts of torpor, and (iii) are adapted to pulsed resources (mast of beech trees). We show here for the first time that maximum T b's in free-living active dormice (during the night) increase regularly and for up to 8 h above 40 °C, which corresponds to slight hyperthermia, probably due to locomotor activity. The highest weekly mean maximum T b was recorded 1 week prior to hibernation (40.45 ± 0.07 °C). At the beginning of the active season and immediately prior to hibernation, the mean maximum T b's were lower. The time dormice spent at T b above 40 °C varied between sexes, depending on mast conditions. The date of parturition could be determined by a sudden increase in mean T b (plus 0.49 ± 0.04 °C). The occurrence of short torpor bouts (<24 h) was strongly affected by the mast situation with much higher torpor frequencies in mast-failure years. Our data suggest that locomotor activity is strongly affected by environmental conditions, and that sexes respond differently to these changes.


Weighted averaging--theory and application to electric response audiometry.
A weighted averaging technique has been developed to overcome the shortcomings of conventional, unweighted averaging in the case of nonstationary noise. The technique is based on the linear least-mean-square estimate of a periodic signal in a simple model of non-stationary noise. This estimate weights each recorded epoch according to the magnitude of the noise within the epoch. In the estimation of a known signal, the weighted averaging procedure yielded smaller root-mean-square errors in comparison with the normal unweighted average. The weighted averaging procedure offers many advantages over conventional averaging or averaging with automatic gain control preamplifiers.


A review of ammonia removal using a biofilm-based reactor and its challenges.
Extensive growth of industries leads to uncontrolled ammonia releases to environment. This can result in significant degradation of the aquatic ecology as well as significant health concerns for humans. Knowing the mechanism of ammonia elimination is the simplest approach to comprehending it. Ammonia has been commonly converted to less hazardous substances either in the form of nitrate or nitrogen gas. Ammonia has been converted into nitrite by ammonia-oxidizing bacteria and further reduced to nitrate by nitrite-oxidizing bacteria in aerobic conditions. Denitrification takes place in an anoxic phase and nitrate is converted into nitrogen gas. It is challenging to remove ammonia by employing technologies that do not incur particularly high costs. Thus, this review paper is focused on biofilm reactors that utilize the nitrification process. Many research publications and patents on biofilm wastewater treatment have been published. However, only a tiny percentage of these projects are for full-scale applications, and the majority of the work was completed within the last few decades. The physicochemical approaches such as ammonia adsorption, coagulation-flocculation, and membrane separation, as well as conventional biological treatments including activated sludge, microalgae, and bacteria biofilm, are briefly addressed in this review paper. The effectiveness of biofilm reactors in removing ammonia was compared, and the microbes that effectively remove ammonia were thoroughly discussed. Overall, biofilm reactors can remove up to 99.7% ammonia from streams with a concentration in range of 16-900 mg/L. As many challenges were identified for ammonia removal using biofilm at a commercial scale, this study offers future perspectives on how to address the most pressing biofilm issues. This review may also improve our understanding of biofilm technologies for the removal of ammonia as well as polishing unit in wastewater treatment plants for the water reuse and recycling, supporting the circular economy concept.


Co-operative binding of triplicate carbohydrate-binding modules from a thermophilic xylanase.
Family 6 carbohydrate-binding modules were amplified by polymerase chain reaction (PCR) from Clostridium stercorarium strain NCIB11754 genomic DNA as a triplet. Individually, these modules bound to xylooligosaccharides and cellooligosaccharides with affinities varying from approximately 3 x 10(3) M(-1) to approximately 1 x 10(5) M(-1). Tandem and triplet combinations of these modules bound co-operatively to soluble xylan and insoluble cellulose to give approximately 20- to approximately 40-fold increases in affinity relative to the individual modules. This co-operativity was an avidity effect resulting from the modules within the tandems and triplet interacting simultaneously with proximal binding sites on the polysaccharides. This occurred by both intrachain and interchain interactions. The duplication or triplication of modules appears to be linked to the growth temperature of the organism; co-operativity in these multiplets may compensate for the loss of affinity at higher temperatures.


Improvement of olfaction in laryngectomized patients with the larynx bypass.
Hyposmia following laryngectomy is an often recognized phenomenon. A larynx bypass device was used to determine whether this olfactory deficit could be reversed simply by restoring nasal airflow. Odorant detection thresholds and confusion matrix identification tests were administered to laryngectomy and normal comparison groups. Data on nasal airflow characteristics with and without the bypass were also analyzed. The results suggested that restoration of nasal airflow completely reversed the hyposmia for trigeminal nerve stimuli. However, the reversal of hyposmia was not complete for those odorants which primarily, if not exclusively, stimulate the olfactory nerve. This suggested that other factors may contribute to laryngectomy-induced hyposmia for olfatory nerve stimuli. Additionally, nasal airflow analysis revealed that confusion matrix identification scores were depedent upon inspiratory sniff flow rates with and without the larynx bypass. It is argued that rehabilitation for the laryngectomee should include efforts to restore and maintain preoperative olfactory acuity.


Magnetic resonance spectroscopy and ambulatory cardiovascular monitoring noninvasively gauge timing of phosphate metabolism and circulation.
Circadian changes in high-energy phosphate metabolism of the human forearm and the relative independence of these metabolic changes from the circulation were noninvasively demonstrated and quantified by combining nuclear magnetic resonance spectroscopy (MRS), ambulatory blood pressure and heart rate monitoring and chronobiologic time series analysis.


Electrophysiological Processes on Motor Imagery Mediate the Association Between Increased Gray Matter Volume and Cognition in Amnestic Mild Cognitive Impairment.
Motor imagery is considered as an ideal window to observe neural processes of action representations. Behavioral evidence has indicated an alteration of motor imagery in amnestic mild cognitive impairment (aMCI). However, it still remains unclear on the altered neurophysiological processing mechanism of motor imagery and whether this mechanism links the abnormal biological basis of motor imagery with impaired cognition in aMCI. This study was to investigate the altered neurophysiological processing mechanism of motor imagery and to examine the relationships between this knowledge and the altered structural basis of motor imagery with impaired cognition in aMCI. A hand mental rotation paradigm was used to manipulate the processing of motor imagery while event-related brain potentials (ERPs) were recorded and gray matter (GM) voxel-based morphometry was performed in 20 aMCI and 29 healthy controls. Compared with controls, aMCI exhibited lower ERP amplitudes in parietal cortex and higher ERP amplitudes in frontal cortex during motor imagery. In addition, aMCI showed reduced GM volumes in cerebellum posterior lobe, insula and hippocampus/parahippocampal gyrus, and increased GM volumes in middle cingulate gyrus and superior frontal gyrus. Most importantly, increased ERP amplitude significantly mediated the association between increased GM and cognition. This study provided a novel evidence for the relationships between the electrophysiological processing mechanism and structural basis of motor imagery with impaired cognition in aMCI. It suggests that improving neural activity by stimulating the frontal lobe can potentially contribute to acquire motor imagery skills for neurological rehabilitation in aMCI subjects.


Studying the impacts of test condition and nonoptimal positioning of the sensors on the accuracy of the in-situ U-value measurement.
The non-destructive thermal characterization of building envelopes relies significantly on various factors such as climate conditions, monitoring devices used, indoor environment, and conditioning systems. In the case of both the temperature-based method (TBM) and heat flux meter (HFM) approaches, U-value is determined considering the ideal condition of steady state. However, it is challenging to accurately define the true thermal condition of buildings when monitoring is affected by inherent uncertainties of the chosen approach and inadequate instrumentation of building envelopes. This paper presents the outcomes of an experimental campaign, that aimed to evaluate the impact of incorrectly positioned exterior sensors, on the precision of U-value measurements. This study simultaneously employed the TBM and HFM approaches. To enhance the accuracy of the results, rigorous outlier detection and statistical analysis were employed on the data collected from three autonomous monitoring systems. The findings of this study revealed that the applied data analysis yielded more satisfactory results for the TBM approach compared to HFM. However, regardless of the approach used, the effectiveness of outlier detection relied heavily on the accuracy of the monitoring systems. When removing an individual outlier, the monitoring systems characterized with higher accuracies provided U-values that were closer to the theoretical values, than less accurate ones.


Out of sight - Out of mind? The need for a professional and standardized peri-mission first responder support model.
First responders are an essential part of the chain (-mail) of survival as they bridge and reduce the time to first chest compressions and defibrillation substantially. However, in the peri-mission phase before and after being sent to a cardiac arrest, these first responders are in danger of being forgotten and taken for granted, and the potential psychological impact has to be remembered. We propose a standardized first responder support system (FRSS) that needs to ensure that first responders are valued and cared for in terms of psychological safety and continuing motivation. This multi-tiered program should involve tailored education and standardized debriefing, as well as actively seeking contact with the first responders after their missions to facilitate potentially needed professional psychological support.


Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation.
Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.


Selection of reference genes for quantitative real-time PCR analysis of photosynthesis-related genes expression in Lilium regale.
Photosynthesis is closely related to the growth of plants. A stable reference gene is fundamental for studies of the molecular mechanism of photosynthesis in Lilium regale. Therefore, it is very important to select a suitable reference gene for qRT-PCR analysis on genes of photosynthetic system, chlorophyll biosynthetic pathway and chloroplast development in Lilium regale. Three kinds of tissues, leaves and bulbs (abnormal leaves) of tissue culture plantlets and cotyledons of seedlings of the wild-type and mutant Lilium regale were selected as materials for qRT-PCR. Six housekeeping genes were selected as candidate genes from transcriptome sequencing data of the wild-type and yellow seedling lethal mutant of Lilium regale. Finally, the expression stability of six candidate reference genes was analyzed using geNorm, NormFinder, and BestKeeper software, the comparative ∆Ct method, and the RefFinder program. The results showed that LrActin2 was the best reference gene for qRT-PCR analysis of photosynthesis-related genes expression in leaves of tissue culture plantlets and seedlings of Lilium regale. This study provided useful data for further research on molecular mechanism of photosynthesis in the Lilium.


Helfrich's concept of intrinsic force and its molecular origin in bilayers and monolayers.
Bilayers and monolayers are excellent models of biological membranes. The constituents of the biological membranes such as lipids, cholesterols and proteins are chiral. Chiral molecules are abundant in nature (protein, nucleic acid and lipid). It is obvious that relationship between chirality and morphology (as well as function) of biological membrane is of interest for its fundamental importance and has technological implication regarding various membrane functions. The recent years have witnessed that a number of experimental studies in biomimetic systems have shown fascinating morphologies where chirality of the constituent molecule has decisive influence. Significant progress is made towards the understanding of these systems from the theoretical and computational studies. Helfrich's concept of intrinsic force arising from chirality is a milestone in understanding the biomimetic system such as bilayer and the related concepts, further progresses in molecular understanding made in recent years and experimental studies revealing the influence of chirality on morphology are the focus of the present review. Helfrich's concept of intrinsic force arising due to chirality is useful in understanding two-dimensional bilayers and one-dimensional monolayers and related mimetic systems. Various experimental techniques are used, which can probe the molecular architecture of these mimetic systems at different length scales and both macroscopic (thermodynamic) as well as microscopic (molecular) theories are developed. These studies are aimed to understand the role of chirality in the molecular interaction when the corresponding molecule is present in an aggregate. When one looks into the variety of morphologies exhibited by three-dimensional bilayer and two-dimensional monolayer, the later types of systems are more exotic in the sense that they show more diversity and interesting chiral discrimination. Helfrich's concept of intrinsic force may be considered useful in both cases. The intrinsic force due to chirality is the decisive factor in determining morphology which is explained by molecular approaches. Finally, biological and technological implications of such morphological variations are briefly mentioned.


Erratum: Downregulation of ubiquitin-specific peptidase 39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells.
[This corrects the article DOI: 10.3892/ol.2018.8061.].


Outcome of tracheostomy after pediatric cardiac surgery.
To investigate the incidence, timing indications and outcome of tracheotomy in children who underwent cardiac surgeries. All pediatric cardiac patients (under 14 years of age) who underwent cardiac surgeries and required tracheotomy from November 2000 to November 2010 were reviewed. The data were collected and reviewed retrospectively. Sixteen children underwent tracheotomy after cardiac surgery. Fifteen of these cases had surgery for congenital heart disease, and one had surgery for an acquired rheumatic mitral valve disease. The mean ± SEMs of the durations of ventilation before and after tracheotomy were 60.4 ± 9.8 and 14.5 ± 4.79 days respectively (P value 0.0002). The means ± SEM of the lengths of ICU stay before and after tracheotomy were 63.31 ± 10.15 and 22 ± 5.4 days respectively (P value 0.0012). After the tracheotomy 12/16 patients (75%) were weaned from their ventilators and 10/16 were discharged from the PCICU. Six patients were discharged from the hospital and 3 were successfully decannulated. The overall survival rate was 9/16 (56%). Tracheostomy shortens the duration of mechanical ventilation and facilitates discharge from the ICU. The mortality of tracheotomy patients is still significant but is mainly related to the primary cardiac disease.


Determination of the level of certain trace elements in vegetables in differently contaminated regions.
The aim of the investigations was the determination of the lead, cadmium, copper, iron, zinc and magnesium content in some vegetables in an industrial region (Cracow) and in an agricultural region far from industrial centres (control). It was found that all the vegetables analysed contained lead and cadmium contaminations. The average lead concentration in parsley-haulm and parsley-root and cadmium concentration in beets, onion, parsley-haulm, leek, lettuce and potatoes coming from the Cracow region exceeded the permissible norm. In the vegetables from the Cracow region the levels of the determined trace elements were higher (P < 0.01) than that of the controls.


Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression.
Increased serum triglyceride levels constitute a risk factor for coronary heart disease. Apolipoprotein CIII (Apo CIII) is a determinant of serum triglyceride metabolism. In this study, we investigated whether activators of the nuclear farnesoid X receptor (FXR) modulate Apo CIII gene expression. The influence of bile acids and synthetic FXR activators on Apo CIII and triglyceride metabolism was studied in vivo by using FXR wild-type and FXR-deficient mice and in vitro by using human primary hepatocytes and HepG2 cells. In mice, treatment with the FXR agonist taurocholic acid strongly decreased serum triglyceride levels, an effect associated with reduced Apo CIII serum and liver messenger RNA levels. By contrast, no change was observed in FXR-deficient mice. Incubation of human primary hepatocytes and HepG2 cells with bile acids or the nonsteroidal synthetic FXR agonist GW4064 resulted in a dose-dependent down-regulation of Apo CIII gene expression. Promoter transfection experiments and mutation analysis showed that bile acid-activated FXR decrease human Apo CIII promoter activity via a negative FXR response element located in the I(4) footprint between nucleotides -739 and -704. Chromatin immunoprecipitation experiments showed that bile acid treatment led to binding of FXR/retinoid X receptor heterodimers to and displacement of HNF4alpha from this site. Bile acid treatment still repressed liver Apo CIII gene expression in hepatic HNF4alpha-deficient mice, suggesting an active rather than a competitive mechanism of Apo CIII repression by the FXR. We identified bile acid and synthetic activators of the nuclear FXR as negative regulators of Apo CIII expression, an effect that may contribute to the triglyceride-decreasing action of FXR agonists.


Quantitative reversed-phase high-performance liquid chromatography of major and modified nucleosides in DNA.
Improved, highly accurate high-performance liquid chromatographic methods for the measurement of the major and modified nucleosides in enzymatic digests of DNA using a single column are described. Four high resolution separation protocols (isocratic, binary, ternary and high speed) with specifically improved selectivity for 5-methyldeoxycytidine (m5dCyd) from Ade, dIno and Guo are presented. From a detailed study of the various factors contributing to the precision and accuracy of the measurement, optimized conditions and quantitative protocols were established. The ternary buffer allows for the first time the determination of N6-methyldeoxyadenosine (m6dAdo) in the same chromatographic analysis with the other deoxyribonucleosides. The binary system allows quantitation of the absolute amounts of each ribo- and deoxyribonucleoside as well as the mole % of each as the second buffer elutes 5'dA and the internal standard 8-bromoguanosine. The isocratic system allows precise quantitation of the mole % of each ribo- and deoxyribonucleoside while eliminating the need for buffer change valves, buffer cycling and column re-equilibration. Also, a high-speed isocratic system is described which permits separation of the deoxyribonucleosides in 6 min. The quantitative, enzymatic hydrolysis of DNA was evaluated by comparing a 40-h, three-enzyme system with a 4-h, two-enzyme procedure. The latter protocol proved to be an excellent hydrolysis method. These high resolution liquid chromatography techniques provide the most precise, sensitive and accurate measurement of m5dCyd available, in a straightforward method using as little as 1 microgram of DNA, and have allowed us to demonstrate: the existence of tissue-specific differences in levels of m5dCyd in DNA of humans, monkeys, rats and mice; that m5dCyd levels in DNA change during fetal development; that genomic undermethylation of DNA is correlated with cancer and the presence of m6dAdo in DNA of thermophilic organisms.


CT scan appearances in Leigh's disease (subacute necrotizing encephalomyelopathy).
Four cases of Leigh's disease (subacute necrotizing encephalomyelopathy), two confirmed at postmortem examination, have been investigated recently by CT scanning. All four showed the same symmetrical areas of low attenuation in the basal ganglia, especially the putamina. These areas corresponded with the typical areas of necrosis seen in this disease. There was also some evidence of atrophic change in the posterior fossa in some cases. This CT scan appearance may be diagnostic in the appropriate clinical context.


Selective electrochemical sensor for copper (II) ion based on chelating ionophores.
Plasticized membranes using 3-(2-pyridinyl)-2H-pyrido[1,2,-a]-1,3,5-triazine-2,4(3H)-dithione (L1) and acetoacetanilide (L2) have been prepared and explored as Cu2+-selective sensors. Effect of various plasticizers, viz. chloronaphthalene (CN), benzyl acetate (BA), o-nitrophenyloctyl ether (o-NPOE), and anion excluders, sodium tetraphenylborate (NaTPB) and oleic acid (OA) was studied in detail and improved performance was observed at several instances. Optimum performance was observed with dithione derivative (L1) having a membrane composition of L1 (5):PVC (120):o-NPOE (240):OA (10). The sensor works satisfactorily in the concentration range 5.0 x 10(-8) to 1.0 x 10(-2) M (detection limit 4.0 x 10(-8) M) with a Nernstian slope of 29.5 mV decade(-1) of activity. Wide pH range (3.0-9.5), fast response time (12s), non-aqueous tolerance (up to 20%) and adequate shelf life (4 months) indicate the vital utility of the proposed sensor. The potentiometric selectivity coefficient values as determined by match potential method (MPM) indicate good response for Cu2+ in presence of interfering ions. The proposed electrode comparatively shows good selectivity with respect to alkali, alkaline earth, transition and some rare earth metals ions. The electrode was used for the determination of copper in different milk powder, water samples and as indicator electrode in potentiometric titration of copper ion with EDTA.


Actions of perchlorate ions on rat soleus muscle fibres.
1. The effects of perchlorate (ClO4-) on contraction have been studied in rat soleus muscle fibres using (i) potassium (K+) contracture and (ii) two-microelectrode-point voltage clamp techniques. 2. Membrane potentials (Vm) at all external [K+] were 3-5 mV more negative in ClO4-. The hyperpolarization could not be attributed to a change in Na+, K+, or Cl- permeability, or to an effect on the Na(+)-K+ pump. 3. ClO4- shifts the voltage dependence of tension activation, and contraction threshold, to more negative membrane potentials without altering maximum tension. Consequently, twitches and submaximal K+ contractures were potentiated, whereas tetanic contractions and 200 mM-K+ contractures were unaltered. 4. The decay of K+ contractures during steady depolarization with ClO4- developed a slow exponential phase with an average time constant of 6.05 +/- 0.76 min at -38 mV, and 1.68 +/- 0.15 min at -19 mV. This slow component was (a) under the rapid control of the surface Vm and (b) did not depend on external Ca2+. 5. Inactivation of E-C coupling was measured with a test 200 mM-K+ depolarization following 3-10 min depolarizations in conditioning solutions containing 20-120 mM-K+. ClO4- induced a negative shift in the curve-relating test K+ contracture amplitude to conditioning Vm but did not alter the rate of repriming of tension upon repolarization. 6. The results suggest that ClO4- increases the amount of activator produced during depolarization and thus allows the slow inactivation step in excitation-contraction (E-C) coupling to be reflected in the decay of K+ contracture tension. 7. A 'perchlorate contracture', which did not depend on the activation of E-C coupling, was observed. The contracture depended on external Ca2+, but not on voltage-dependent Ca2+ channels or Na(+)-Ca2+ exchange.


Direct observation of single-charge-detection capability of nanowire field-effect transistors.
A single localized charge can quench the luminescence of a semiconductor nanowire, but relatively little is known about the effect of single charges on the conductance of the nanowire. In one-dimensional nanostructures embedded in a material with a low dielectric permittivity, the Coulomb interaction and excitonic binding energy are much larger than the corresponding values when embedded in a material with the same dielectric permittivity. The stronger Coulomb interaction is also predicted to limit the carrier mobility in nanowires. Here, we experimentally isolate and study the effect of individual localized electrons on carrier transport in InAs nanowire field-effect transistors, and extract the equivalent charge sensitivity. In the low carrier density regime, the electrostatic potential produced by one electron can create an insulating weak link in an otherwise conducting nanowire field-effect transistor, modulating its conductance by as much as 4,200% at 31 K. The equivalent charge sensitivity, 4 × 10(-5) e Hz(-1/2) at 25 K and 6 × 10(-5) e Hz(-1/2) at 198 K, is orders of magnitude better than conventional field-effect transistors and nanoelectromechanical systems, and is just a factor of 20-30 away from the record sensitivity for state-of-the-art single-electron transistors operating below 4 K (ref. 8). This work demonstrates the feasibility of nanowire-based single-electron memories and illustrates a physical process of potential relevance for high performance chemical sensors. The charge-state-detection capability we demonstrate also makes the nanowire field-effect transistor a promising host system for impurities (which may be introduced intentionally or unintentionally) with potentially long spin lifetimes, because such transistors offer more sensitive spin-to-charge conversion readout than schemes based on conventional field-effect transistors.


Development and repair of blood vessels in the zebrafish spinal cord.
The vascular system is inefficiently repaired after spinal cord injury (SCI) in mammals, resulting in secondary tissue damage and immune deregulation that contribute to the limited functional recovery. Unlike mammals, zebrafish can repair the spinal cord (SC) and restore motility, but the vascular response to injury has not been investigated. Here, we describe the zebrafish SC blood vasculature, starting in development with the initial vessel ingression in a body size-dependent manner, the acquisition of perivascular support and the establishment of ventral to dorsal blood circulation. The vascular organization grows in complexity and displays multiple barrier specializations in adulthood. After injury, vessels rapidly regrow into the lesion, preceding the glial bridge and axons. Vascular repair involves an early burst of angiogenesis that creates dysmorphic and leaky vessels. Dysfunctional vessels are later removed, as pericytes are recruited and the blood-SC barrier is re-established. This study demonstrates that zebrafish can successfully re-vascularize the spinal tissue, reinforcing the value of this organism as a regenerative model for SCI.


Purification and characterization of a non-reconstitutable azurin, obtained by heterologous expression of the Pseudomonas aeruginosa azu gene in Escherichia coli.
The azurin-encoding azu gene from Pseudomonas aeruginosa was cloned and expressed in Escherichia coli. A purification procedure was developed to isolate the azurin obtained from the E. coli cells. No differences were observed between azurins isolated from P. aeruginosa and E. coli. A non-reconstitutable azurin-like protein, azurin*, with a spectral ratio (A625/A280) less than 0.01 could be separated from holo-azurin with a spectral ratio of 0.58 (+/- 0.01). The properties of azurin* were examined by electrophoretic (SDS-PAGE and IEF) and spectroscopic (UV/vis, 1H-NMR, static and dynamic fluorescence) techniques, and compared to the properties of holo-azurin and apo-azurin. Azurin* resembles apo-azurin (same pKa* values of His-35 and His-117, same fluorescence characteristics). However, it has lost the ability to bind Cu-ions. It is tentatively concluded that azurin* is a chemically modified form of azurin, the modification possibly being due to oxidation of the ligand residue Cys-112 or the formation of a chemical bond between the ligand residues Cys-112 and His-117. In agreement with previous results from Hutnik and Szabo (Biochemistry (1989) 28, 3923-3934), fluorescence experiments show that the heterogeneous fluorescence decay observed for holo-azurin is not due to the presence of azurin*, but most likely originates from conformational heterogeneity of the holo-azurin.


P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation.
The crosstalk between the P2Y(2) G-protein-coupled receptor (GPCR) with TrkA receptor tyrosine kinase (RTK) is an important mechanism that regulates neuronal differentiation. We show that Src family kinases (SFK) regulate P2Y(2)-TrkA molecular crosstalk. SFK inhibitors block ATPgammaS/P2Y(2)-promoted enhancement of NGF/TrkA signaling and neuronal differentiation in PC12 cells, abrogate the enhancement by ATPgammaS of neurite outgrowth in primary cultures of dorsal root ganglion neurons, and block co-immunoprecipitation of TrkA, P2Y(2) receptors and SFK. These results identify SFK as mediating nucleotide-enhanced neurotrophin-dependent neuronal differentiation and thus, as a key convergence point for interaction between RTKs and GPCRs.


The role of image-guided radiotherapy in prostate cancer: A systematic review and meta-analysis.
Image-guided radiotherapy (IGRT) has gradually been widely promoted in clinical procedure. However, there has been no consensus on the effects of IGRT on toxicity and survival, and no clear level 1 evidence has even been promulgated. Medline, EMBASE, PubMed, Cochrane databases and ClinicalTrials.gov were searched for studies comparing IGRT vs non-IGRT or higher frequency IGRT vs lower frequency IGRT during prostate radiotherapy, indexed from database inception to April 2022. The review included 18 studies (3 randomized clinical trial and 15 cohort studies) involving 6521 men, with a median duration of patient follow-up of 46.2 months in the IGRT group vs 52.7 months in the control group. The meta-analysis demonstrated that IGRT significantly reduced acute GU (risk ratio [RR], 0.78; 95 % confidence interval [CI], 0.69-0.88; P < 0.001 [9 studies]) and GI toxicity (RR, 0.49; 95 % CI, 0.35-0.68; P < 0.001 [4 studies]) and late GI toxicity (HR, 0.25; 95 % CI, 0.07-0.87; P = 0.03 [3 studies]) compared with non-IGRT. Meanwhile, compared with prospective studies, retrospective studies showed that IGRT had a more significant effect in reducing the late GI toxicity. Compared with non-daily IGRT, daily IGRT significantly improved 3-year PRFS (HR, 0.45; 95 % CI, 0.28-0.72; P = 0.001 [2 studies]) and BFFS (HR, 0.57; 95 % CI, 0.39-0.83; P = 0.003 [3 studies]). Furthermore, high-frequency daily IGRT could lead to greater 3-year BFFS benefit in prostate cancer patients than weekly IGRT. However, no significant effects of IGRT on acute rectal toxicity, late GU toxicity, 5-year OS and SCM were found. For men receiving prostate radiotherapy, IGRT was associated with an improvement in biochemical tumor control and a reduction in GI and acute GU toxicity, but did not significantly improve 5-year OS or increase 5-year SCM.


Psychometric Evaluation of the Prenatal Attitudes Toward Motherhood and Pregnancy Scale in an Iranian Population.
Background and Purpose: Mothers' attitudes toward motherhood and pregnancy are crucial to their ability to adjust themselves to motherhood. Attitudes toward motherhood and pregnancy questionnaire (PRE-MAMA) have been used in a few Iranian studies, and its validity and reliability have not been assessed yet. This study, hence, aimed to provide the psychometric properties of the PRE-MAMA in Iran. Methods: In this research, 110 pregnant women were selected through random sampling in 2020. The face, content, and construct validity of the PRE-MAMA were examined through exploratory and confirmatory analyses. The test-retest reliability and internal consistency were also employed to assess the reliability of the questionnaire. Results: The content validity index and content validity ratio of the PRE-MAMA were 0.98 and 0.97, respectively. The results of the scale-based exploratory factor analysis confirmed the two-factor structure of the questionnaire. The Cronbach's alpha coefficient was 0.63, and the intraclass correlation coefficient (95% Confidence Interval [CI]) was equal to 0.97 (.93-.99). Conclusion: The Iranian version of PRE-MAMA is a valid and reliable tool for assessing Iranian mothers' attitudes toward motherhood and pregnancy.


Deviating vital signs in continuous monitoring prior to discharge and risk of readmission: an observational study.
Premature discharge may result in readmission while longer hospitalization may increase risk of complications such as immobilization and reduce hospital capacity. Continuous monitoring detects more deviating vital signs than intermittent measurements and may help identify patients at risk of deterioration after discharge. We aimed to investigate the association between deviating vital signs detected by continuous monitoring prior to discharge and risk of readmission within 30 days. Patients undergoing elective major abdominal surgery or admitted with acute exacerbation of chronic obstructive pulmonary disease were included in this study. Eligible patients had vital signs monitored continuously within the last 24 h prior to discharge. The association between sustained deviated vital signs and readmission risk was analyzed by using Mann-Whitney's U test and Chi-square test. A total of 51 out of 265 patients (19%) were readmitted within 30 days. Deviated respiratory vital signs occurred frequently in both groups: desaturation < 88% for at least ten minutes was seen in 66% of patients who were readmitted and in 62% of those who were not (p = 0.62) while desaturation < 85% for at least five minutes was seen in 58% of readmitted and 52% of non-readmitted patients (p = 0.5). At least one sustained deviated vital sign was detected in 90% and 85% of readmitted patients and non-readmitted patients, respectively (p = 0.2). Deviating vital signs prior to hospital discharge were frequent but not associated with increased risk of readmission within 30 days. Further exploration of deviating vital signs using continuous monitoring is needed.


Parameters for DNA vaccination using adaptive constant-current electroporation in mouse and pig models.
Enhancing the expression of DNA vaccines requires that specific conditions of delivery are optimized. We describe experiments using adaptive constant-current electroporation (EP) in mice and pigs examining parameters such as target muscle, delay between plasmid delivery and onset of EP pulses and DNA vaccine formulation; our studies show that concentrated formulations result in better expression and immunogenicity. Furthermore, various conditions of EP that limit the amount of muscle damage were measured. The results of these studies will help to advance the success of DNA vaccines in animals into success in human clinical trials.


Invasive trichosporonosis in an AIDS patient: case report and review of the literature.
Invasive Trichosporon infection is a rare, life-threatening infection in immunocompromised patients. It has been reported as an emerging opportunistic infection in those with acquired immune deficiency syndrome (AIDS). Only 12 cases of invasive trichosporonosis in patients with HIV have been documented, none in Southeast Asia. We report a case of fatal, disseminated trichosporonosis in a Filipino AIDS patient with severe cutaneous and pulmonary involvement. Invasive trichosporonosis should be considered in HIV-positive patients with disseminated fungal infection since this may be refractory to conventional antifungal treatment.


Restricted feeding does not modify discriminative stimulus effects of morphine in the rat.
An experiment was performed to determine if the discriminative stimulus effects of morphine are modified by mild food deprivation, a condition that increases drug-reinforced behavior. Rats were trained to discriminate between SC injections of saline and morphine (3.0 mg/kg) in a discrete-trial shock-avoidance procedure. Stimulus generalization curves for morphine were then determined on three occasions by a cumulative-dosing procedure: before, during and after the body weight of the rats had been reduced to 86-87% of normal by restricted feeding. Food deprivation had little or no effect on the morphine generalization curve. Despite a close relationship between the reinforcing and discriminative stimulus properties of opioid drugs, stimulus control of behavior by morphine was not modified by a condition that enhances opioid-reinforced behavior.


A pay-for-performance system for civil service doctors: the Indonesian experiment.
In 1980 the Government of Indonesia proposed the introduction of a pay-for-performance system, the Functional Position System (FPS), for certain occupational categories of civil servants to provide a career development path and stimulate productivity (Government of Indonesia. Government Ordinance No. 3, 1980 Concerning Appointment to Civil Service Rank. Jakarta, 1980). The FPS, a bold pay concept in the civil service, links pay to skills and performance. In 1987, instructions were issued for doctors to be included in the system (Government of Indonesia, Credit Scores for Doctors. Circular Issued by the Ministry of Health and the Agency for Administration of the Civil Service No. 614/MENKES/E/VIII/1987 and No. 16/SE/1987). In this paper we evaluate how well the system-which in principle could be applicable to both developed and developing economies--can meet its stated objectives for Indonesian doctors working in the community, and for Indonesian health policy objectives as stated in the country's last five-year development plan "Repelita V" (Government of Indonesia. The Fifth Five-year Development Plan (Repelita V) 1989-1994. Jakarta, Indonesia, 1989). The FPS is particularly innovative in the Indonesian environment where wages are low and comparatively uniform, reflecting a philosophy of 'shared poverty', and vary primarily by seniority. The FPS has, however, several conceptual and practical shortcomings. The design of the reward system disregards effort or time inputs, as well as other inputs needed per unit of reward. Consequently, the FPS can not be used as an effective incentive system promoting professional excellence and health policy objectives. Practically, the system hardly provides an effective alternative for career development among community physicians.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes.
Estrogen exposure and metabolism may play an important role in the development of estrogen-sensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models. One-hundred-eighty-one female cynomolgus macaques were randomized to receive OC or nothing for 26 months premenopausally, then ovariectomized and randomized to one of three diets for 36 months: an IF-depleted soy protein isolate (Soy-) diet, a Soy diet with IF (Soy+), or a Soy- diet supplemented with conjugated equine estrogens (CEE). Prior OC-treatment significantly reduced CYP gene expression in the mammary gland (< or =60% of OC-). Dietary IFs had no effect on CYP expression, while CEE-treatment decreased CYP1A1 and increased CYP3A4 mRNA in a tissue-specific manner. For in vitro studies, we measured effects of the isoflavonoids genistein, daidzein and equol on CYP activity using intact V79 cells stably transfected to express CYP1A1, CYP1B1, or CYP3A4. All three IFs significantly altered CYP activity in a dose-dependent and isoform-specific manner (20-95% inhibition versus controls). These results suggest potential mechanisms for prior OC and dietary IF effects on cancer risk in estrogen-responsive tissues.


Toxicity of profenofos to the springtail, Folsomia candida, and ammonia-oxidizers in two agricultural soils.
Extensive use of organophosphorus insecticide profenofos (PFF) for agricultural and house-hold purposes has led to serious environmental pollution, with potential risk to organisms in the ecosystem. This study examined the toxicity of PFF to the soil springtail Folsomia candida and ammonia-oxidizers through a series of toxicity tests conducted on two agricultural soils. It was found that the survival, reproduction, hsp70 gene expression of F. candida and the soil potential nitrification rate (PNR) were sensitive to the PFF, whereas no apparent change was observed in the abundance of ammonia-oxidizers. The reproduction of F. candida was the most sensitive endpoint (mean 0.10 mg/kg of EC(50) value) for PFF, although the test was more time-consuming. The results of the acute toxicity tests suggested that the survival of F. candida could be considered as the most suitable bioindicator for fast screening of PFF toxicity because of its fast and easy test procedure. In addition, the hsp70 gene expression in F. candida and the PNR could be used as important parameters for assessment of PFF toxicity. The threshold concentration based on the obtained endpoints differed in the two soils, and consequently the soil property should be considered in toxicity assessments of contaminated soils.


Hypernephroma presenting as acute delirium.
We report a case of hypernephroma that presented as acute delirium. There was no evidence of central nervous system metastatic disease and the delirium resolved upon removal of the tumor.


Effects of saline water on soil properties and red radish growth in saline soil as a function of co-applying wood chips biochar with chemical fertilizers.
Currently, using unconventional water sources in agriculture has become necessary to face overpopulation worldwide. Therefore, a pot experiment was carried out to evaluate the effects of irrigation with saline water in the presence of co-applied wood chips biochar (WCB) with chemical fertilizers on physicochemical properties and nutrient availability as well as growth parameters, and yield of red radish (Raphanus sativus L.) grown in the saline sandy soil. The WCB was added to the saline sandy soil at levels of 0 (control), 2.5, and 5% w/w. Then, this soil was cultivated by red radish plants and irrigated with saline water (5 dS m- 1). This experiment was performed in a randomized complete block design with three replicates. Compared with the control treatment, WCB treatments increased significantly soil water holding capacity by 34.8% and 73.2% for levels of 2.5 and 5%, respectively. Soil pH decreased significantly in all WCB treatments. The relative increase in the total available nitrogen over the control was 30.1 and 103.5% for 2.5 and 5% wood chips biochar, respectively. Compared to the control, applying WCB at 2.5% led to an increase in the fresh root weight of red radish plants by 142.7%, while 5% caused a decrease in the fresh root weight of red radish plants by 29.4%. Recently, WCB represents an interesting approach to the rehabilitation of saline soils and the management of using saline water sources. It is recommended that combined application of WCB at a level of 2.5% with chemical fertilizers in order to improve red radish growth and nutrient retention in the saline sandy soil which preserves the ecosystem as well as increases productivity leading to the reduction of costs.


Postprandial studies on dietary cholesterol in human subjects using stable isotopes and gas chromatography-mass spectrometry analysis.
We hypothesized that intestinal absorption and postprandial re-secretion of dietary cholesterol may be a particularly complex process in humans. To test this hypothesis, we used deuterium-enriched cholesterol to specifically label meal cholesterol and developed an improved method for quantitative measurement of traces of deuterated cholesterol as well as cholesterol with reference to two different internal standards by gas chromatography-mass spectrometry (GC-MS) measurement. In the first study, a group of healthy subjects ingested a single test meal containing deuterated cholesterol with a 7 h postprandial follow-up. In the second one, a group of healthy subjects ingested a first test meal containing deuterated cholesterol and a follow-up was performed during three consecutive test meals and later until 72 h. The most striking observations were that the occurrence of dietary cholesterol in chylomicrons is not concomitant to triglycerides and is very low after a single meal while most dietary cholesterol is re-secreted in chylomicrons after a second, and even a third, fat test meal. The data obtained show that the re-secretion of dietary cholesterol from the small intestine is a slow and complex process in humans.


Murine response to the opportunistic bacterium Pseudomonas aeruginosa infection in gut dysbiosis caused by 5-fluorouracil chemotherapy-induced mucositis.
This manuscript aims to explain the relationship between mucositis caused by 5-FU over gut bacterial species and susceptibility to opportunistic infection caused by P. aeruginosa. BALB/c mice were intraperitoneally treated with PBS or 5-FU. Bodyweight and faecal consistency were checked daily. Mice faecal DNA was extracted, and bacterial phylogenetic groups were analysed using qPCR or high-throughput sequencing. Immunofluorescence was used to evaluate BMDM activation by mice-treated faecal content. Mice were challenged intratracheally with virulent P. aeruginosa, and the CFU and histology were analysed. Faecal microbiota were transplanted to evaluate the gut microbiota and resistance to pulmonary P. aeruginosa recovery. The animals treated with 5-FU presented mucositis with great weight loss, altered faecal consistency, bacterial gut dysbiosis and histological changes in the intestinal mucosa. Mice under 5-FU treatment were more susceptible to lung infection by the bacteria P. aeruginosa and had more extensive tissue damage during their lung infection with greater pro-inflammatory gene expression. It was observed that the mucositis remained in the groups with 5-FU even with the FMT. The results caused by mucositis in animals that received allogeneic FMT were reversed, however, with a decrease in P. aeruginosa susceptibility in animals treated with 5-FU and allogeneic FMT compared to animals treated with 5-FU and autologous FMT. Treatment with 5-FU in a murine model makes it more susceptible to pulmonary infection by the bacterium P. aeruginosa, FMT offers an opportunity to protect against this susceptibility to infection.


The role of RNA polymerase initiation and elongation in control of total RNA and histone mRNA synthesis in sea urchin embryos.
The involvement of RNA polymerase initiations in regulating total RNA synthesis and the synthesis of the early histone mRNAs was investigated. Nuclei were isolated from developing sea urchin embryos from 4- to 600-cell stages, and the transcription of already initiated polymerase complexes was studied in a "run-off," or elongation, assay; this assay was optimized by using high levels of ribonucleoside triphosphates. Under these conditions the relative levels of RNA synthesis in isolated nuclei from different stages closely paralleled the known rates of synthesis in vivo. However, if sarkosyl is included in the elongation assay, the nuclei of older stages display greatly stimulated synthesis while early cleavage stage nuclei are not stimulated. Sarkosyl does not reveal any elongated transcripts from the early histone genes in nuclei from later stages of development. This has been interpreted to mean that there are many initiated polymerase II complexes that do not elongate rapidly at later stages, but the early histone genes are inactive at later stages because they do not possess any productively initiated polymerases.


Magnesium absorption from mineral water decreases with increasing quantities of magnesium per serving in rats.
It is hypothesized that magnesium (Mg) absorption from mineral water is affected by the concentration of Mg in the water, the consumption pattern, and the volume consumed per serving. The present study examined the effect of serving volume and consumption pattern of artificial mineral water (AMW) and Mg concentration on Mg absorption in rats. Magnesium in AMW was labeled with magnesium-25 as a tracer. Each group consisted of 6 or 7 rats. In experiment 1, the rats received 1 mL of AMW containing 200 mg Mg/L at 4 times, 400 mg Mg/L twice, or 800 mg Mg/L at 1 time. In experiment 2, the rats received 1 mL of AMW containing 200 mg Mg/L or 0.25 mL of AMW containing 800 mg Mg/L at 4 times or 1 mL of AMW containing 800 mg Mg/L at 1 time. The absorption of Mg decreased with increasing Mg concentrations in the same serving volume of AMW with different serving frequencies. When the AMW containing 800 mg Mg/L was portioned into 4 servings, Mg absorption increased to the level of absorption in the group exposed to AMW containing 200 mg Mg/L served at the same frequency. These results suggest that the Mg concentration and the volume of AMW do not affect Mg absorption per se, but Mg absorption from AMW decreases when the amount of Mg in each serving is increased. Thus, frequent consumption is preferable for mineral water rich in Mg when the total consumption of mineral water is the same.


The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review.
Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.


Freeze-thaw revival of rotifers and algae in a desiccated, high-elevation (5500 meters) microbial mat, high Andes, Perú.
This is the first study of the highest elevation cyanobacteria-dominated microbial mat yet described. The desiccated mat was sampled in 2010 from an ephemeral rock pool at 5500 m above sea level in the Cordillera Vilcanota of southern Perú. After being frozen for 6 years at -20 °C in the lab, pieces of the mat were sequenced to fully characterize both the 16 and 18S microbial communities and experiments were conducted to determine if organisms in the mat could revive and become active under the extreme freeze-thaw conditions that these mats experience in the field. Sequencing revealed an unexpectedly diverse, multi-trophic microbial community with 16S OTU richness comparable to similar, seasonally desiccated mats from the Dry Valleys of Antarctica and low elevation sites in the Atacama Desert region. The bacterial community of the mat was dominated by phototrophs in the Cyanobacteria (Nostoc) and the Rhodospirillales, whereas the eukaryotic community was dominated by predators such as bdelloid rotifers (Philodinidae). Microcosm experiments showed that bdelloid rotifers in the mat were able to come out of dormancy and actively forage even under realistic field conditions (diurnal temperature fluctuations of -12 °C at night to + 27 °C during the day), and after being frozen for 6 years. Our results broaden our understanding of the diversity of life in periodically desiccated, high-elevation habitats and demonstrate that extreme freeze-thaw cycles per se are not a major factor limiting the development of at least some members of these unique microbial mat systems.


Metal artifacts of hip arthroplasty implants at 1.5-T and 3.0-T: a closer look into the B1 effects.
To evaluate the effect of circular polarization (CP) and elliptical polarization (EP) of the B1 field on metal implant-induced artifacts of titanium (Ti) and cobalt-chromium (CoCr) hip arthroplasty implants at 1.5-T and 3.0-T field strengths. In vitro Ti and CoCr total hip arthroplasty implants were evaluated using high transmit and receive bandwidth turbo spin echo (HBW-TSE) and slice encoding for metal artifact correction (SEMAC) metal artifact reduction techniques. Each technique was implemented at 1.5-T, which only allows for CP of B1 field as the system default, as well as 3.0-T, which permitted CP and EP. Manual segmentation quantified the size of the metal artifacts at the level of the acetabular cup, femoral neck, and femoral shaft. In the acetabular cup and femoral neck, 1.5-T CP achieved smaller artifact sizes than 3.0-T CP (28-29% on HBW-TSE, p = 0.002-0.005; 17-34% on SEMAC, p = 0.019-0.102) and 3.0-T EP (25-28% on HBW-TSE, p = 0.010-0.011; 14-36% on SEMAC, p = 0.058-0.135) techniques. In the femoral stem region, 3.0-T EP achieved more efficient artifact suppression than 3.0-T CP (HBW-TSE 44-45%, p < 0.001-0.022; SEMAC 76-104%, p < 0.001-0.022) and 1.5-T CP (HBW-TSE 76-96%, p < 0.001-0.003; SEMAC 138-173%, p = 0.003-0.005) techniques. Despite slightly superior metal reduction ability of the 1.5-T in the region of the acetabular cup and prosthesis neck, 3.0-T MRI of hip arthroplasty implants using elliptically polarized RF pulses may overall be more effective in reducing metal artifacts than the current standard 1.5-T MRI techniques, which by default implements circularly polarized RF pulses.


Mobile Applications Improve Quality of Life on Citizens with Disorientation: The 'NeverLost App' Paradigm.
Mobile technology has been evolved as an important tool in healthcare. Mobile applications are being designed in order to assist patients in their everyday life and also to play a vital role on the improvement of their everyday activities and quality of life. Meanwhile students use advanced techniques in order to design and implement high quality applications that aim to introduce them to the advantages of the mobile technology. In this paper we present the steps for the creation of the application NeverLost that was inspired, designed, created and tested by students of the Secondary Education. NeverLost is an Android application that helps individuals (mainly children) with disabilities, as well as older patients with lack of orientation manage their day-to-day activities. A research of the general benefits that students using this app is presented, as well as their future proposals for the evolution of the app in other aspects of healthcare and quality of life of senior citizens or patients with neurodegenerative diseases.


Sterically hindered analogues of diacylglycerols. Synthesis, binding to the phorbol ester receptor and metabolism in A549 human lung carcinoma cells.
The 5 following compounds were synthesized in order to investigate the relationship between structure and ability of glyceride-type molecules to bind to the phorbol ester receptor: one dioctanoyl cyclohexane-1,2,4-triol, 2 isomeric methyl analogues of 1,2-dioctanoyl-sn-glycerol (diC8), one dimethyl and one cyclohexyl analogue of diC8. Their ability to compete with 3H-labelled phorbol-12,13-dibutyrate [( 3H]PDBu) for specific binding sites in intact A549 human-derived lung carcinoma cells and in a cytosolic cell extract was compared with that of diC8 and 12-O-tetradecanoylphorbol-13-acetate (TPA). The affinity of diC8 for the phorbol ester receptor was much weaker than that of TPA. The analogues in turn were less able than diC8 to compete with [3H]PDBu for receptor sites. Like diC8 and unlike TPA, the synthesized compounds inhibited cell growth only at those concentrations at which cytotoxicity was also apparent. DiC8 and its methyl and dimethyl derivates, but not the cyclohexyl derivative or the cyclohexanetriol diester, were metabolically removed from cellular incubates as measured by gas liquid chromatography. The results suggest that the binding of glyceride-type molecules to the phorbol ester receptor exhibits stringent specificity and that the design of novel potent agonists of phorbol esters might require the placement of the molecular features of diacylglycerols important for biological activity into a molecular framework which is more complicated than glycerol.


Pregnant women's and policymakers' preferences for the expansion of noninvasive prenatal screening: A discrete choice experiment approach study.
Quantitative approaches for eliciting preferences for new interventions are mostly conducted by patients and rarely by policymakers. This study aimed to quantify the preferences of pregnant women and policymakers regarding the addition of a new test to prenatal screening programs for detecting chromosomal abnormalities. A discrete choice experiment was conducted to measure the respondents' preferences for a new prenatal test. A seven-attribute instrument was built based on interviews with pregnant women and policymakers. The data were analyzed using robust conditional logistic regression and nested logit models. In total, 272 pregnant women and 24 policymakers completed the questionnaire (response rates of 48% and 55%, respectively). Overall, all attributes were statistically significant in the pregnant women group, whereas only three attributes (test performance, degree of test result certainty, and cost) were statistically significant in the policymakers group. Statistically significant differences in test performance and information were observed between the two groups. Policymakers differed from pregnant women in their appraisal of attributes related to their preference for a new prenatal screening intervention. The low response rates observed in both groups suggest that further investigation of the relevance of this approach must be conducted.


Assessment of deep learning assistance for the pathological diagnosis of gastric cancer.
Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P = 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P = 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P = 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P = 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.


Measles immunisation non-acceptance: validation of computer-held records and raising the vaccine uptake at early school age; the Maidstone experience.
The parents of all 977 resident children born in 1981 and 1982 recorded as not having received measles vaccine were contacted by letter. They were strongly advised to seek immunisation for their children and asked to complete and return a reply-paid questionnaire. Details of their children's immunisation status, reasons for non-immunisation and history of measles infection were sought, and whether they then intended to have their children immunised. The response rate was 53.3%. Of responders, 27% claimed to have written evidence that their children had already been immunised, the majority of them having been done outside the District. There was a high degree of mobility, mainly into the District, emphasising the need to record immunisation status when registering newly arrived children. The main reasons for non-immunisation were: a history of measles infection, personal or family history of fits or allergy, and mistrust of the vaccine. Many parents had been inappropriately advised by health professionals. 78 children from these cohorts are now known to have been vaccinated in the three months following the mailing and these together with the validation exercise have raised vaccination cover for 1981-born children from 74.7% to 78.9% and for 1982-born children from 77.0% to 81.4%.


"He Will Not Leave Us Alone and I Need the Courts to Help": Defendants' Use of Nonphysical Violence in Domestic Violence Protective Order Cases.
District court judges who make final determinations in domestic violence protective order (DVPO) cases in North Carolina indicate often using heuristics, such as the presence of visible injury, to guide their assessment of violence severity. This approach is concerning as it minimizes nonphysical intimate partner violence. We conducted a thematic analysis of DVPO plaintiff complaints to identify the types of nonphysical vioence described and its effects on plaintiff health outcomes. Most case files included descriptions of nonphysical violence and plaintiffs described fear as a significant mental health outcome. Findings highlight the potentially deleterious impact of nonphysical violence on the well-being of DVPO plaintiffs.


Time study of patient movement through the emergency department: sources of delay in relation to patient acuity.
A continuous observation time study was used to track 1,568 patients through various stages of emergency department care in order to identify sources of delay. Patients initially were assigned to one of four categories of decreasing acuity, and flow profiles were compared for each category. Patients with lowest acuity level experienced long delays in moving through the ED, although the actual evaluation and treatment time was brief. Urinalyses, procedures, radiographs, and blood tests had an increasing impact on treatment times (45 minutes, 63 minutes, 65 minutes, and 126 minutes, respectively, compared to 31 minutes with no tests or procedures). Patients of increasing acuity moved more quickly, but with a longer evaluation and treatment time. The most critical patients moved most quickly but with a brief evaluation and treatment time due to a rapid disposition from the ED or death. This relationship suggests an emergency care system that is oriented toward the efficient care of high-acuity patients but that is less effective for low-acuity patients. This occurs despite the fact that low-acuity patients comprise the vast majority of the ED census, and represent a group for whom delay is a frequent source of patient dissatisfaction.


Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney.
The chemokine CXCL16 plays an important role in the recruitment of leukocytes to sites of inflammation influencing the course of experimental glomerulonephritis. Here we show that human kidneys highly express CXCL16 in the distal tubule, connecting tubule and principal cells of the collecting duct with weak expression in the thick ascending limb of Henle. Beside the membrane localization, a soluble form of CXCL16 can be proteolytically released which acts as a chemotactic factor. In human renal tissue the expression pattern of the disintegrin-like metalloproteinase ADAM10 is similar to that of CXCL16, suggesting ADAM10 can potentially cleave CXCL16 in vivo. When we tested this in primary tubular cells we found that blockade of ADAM10 activity inhibited the IFN-gamma induced release of soluble CXCL16. Acute tubular damage in renal allografts was associated with elevated urinary CXCL16 and this correlated with focally increased apical CXCL16 expression in the distal tubules and collecting ducts. Renal allograft biopsies, with a histopathological diagnosis of acute interstitial rejection, showed increased basolateral ADAM10 expression together with high numbers of infiltrating T cells. Our results suggest that CXCL16 and ADAM10 are involved in the recruitment of T cells to the kidney and play an important role in inflammatory kidney diseases.


Exposure of nonsmoking women to environmental tobacco smoke: a 10-country collaborative study.
The interpretation and interpretability of epidemiologic studies of environmental tobacco smoke (ETS) depend largely on the validity of self-reported exposure. To investigate to what extent questionnaires can indicate exposure levels to ETS, an international study was conducted in 13 centers located in 10 countries, and 1,369 nonsmoking women were interviewed. The present paper describes the results of the analysis of self-reported recent exposure to ETS from any source in relation to urinary concentrations of cotinine. Of the total, 19.7 percent of the subjects had nondetectable cotinine levels, the median value was 6 ng/mg, and the cut-point of the highest decile was 24 ng/mg. The proportion of subjects misreporting their active smoking habit was estimated at between 1.9 and 3.4 percent, depending on whether cut-points of 50 or 100 ng/mg creatinine were used. Large and statistically significant differences were observed between centers, with the lowest values in Honolulu, Shanghai, and Chandigarh, and the highest in Trieste, Los Angeles, and Athens. Mean cotinine/creatinine levels showed a clear linear increase from the group of women not exposed either at home or at work, to the group of those exposed both at home and at work. Values were significantly higher for women exposed to ETS from the husband but not at work, than for those exposed at work but not from the husband. The results of linear regression analysis indicated that duration of exposure and number of cigarettes to which the subject reported being exposed were strongly related to urinary cotinine. ETS exposure from the husband was best measured by the number of cigarettes, while exposure at work was more strongly related to duration of exposure. After adjustment of number of cigarettes for volume of indoor places, a similar increase in cotinine (5 ng/mg) was predicted by the exposure to 7.2 cigarettes/8 h/40 m3 from the husband and 17.9 cigarettes/8 h/40 m3 at work. The results indicate that, when appropriately questioned, nonsmoking women can provide a reasonably accurate description of ETS exposure. Assessment of individual exposure to ETS should focus on daily duration and volume of indoor places where exposure occurred.


Early life experiences: Meaningful differences within and between families.
Previous research has focused on differences in early life experiences that occur between families and their impact on children's development. However, less is known about the variations in early life experiences that occur within families. Here, 53 British mothers (mean age = 34.46 years; SD = 4.35) of newborn infants (mean age = 1.68 months, SD = 0.96) used a smartphone application (app) to repeatedly rate their wellbeing and support and to report their baby's and their own dietary and sleeping patterns (4 app alerts per week for 3 weeks; 12 assessments in total). We found that the app was a practicable tool for observing early life experiences, and that early life experiences differed on average to a greater extent within, rather than between families (59% versus 41% of the total variance). We also found preliminary evidence for meaningful associations among contemporaneous within-family variations in early life experiences.


Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium.
Xanthine oxidase, an iron-sulfur molybdenum flavoprotein known to generate superoxide radical, was demonstrated in several bovine tissues. The enzyme (155 kd polypeptide) was purified from bovine milk lipid globules and antibodies were raised that allowed precipitation of the enzyme without inactivation of enzymatic activity. By immunolocalization techniques at light and electron microscope levels, the antigen was found in milk-secreting epithelial cells but not in epithelial cells of several other tissues. In a number of tissues, including mammary gland, liver, heart, lung and intestine, antibodies to xanthine oxidase stained only endothelial cells of capillaries, including sinusoids, but not endothelia of larger blood vessels and endocard. In both milk-secreting epithelial and capillary endothelial cells, xanthine oxidase was distributed throughout the cytoplasm. Results from biochemical and immunological studies suggest that xanthine oxidase is similar in the various tissues examined and may serve similar redox functions.


The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19.
Elevated bile acid (BA) concentrations in the liver is associated with severe disease, including cholestasis and hepatocellular carcinoma. The nuclear Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the ileum, BA-dependent FXR activation induces the production of the fibroblast growth factor FGF19, a hormone that reaches the liver through the portal system where it represses the expression of CYP7A1, the rate limiting enzyme in the process of hepatic BAs synthesis. This gut-liver FXR-FGF19 dual action is the paradigm of physiological BA regulation and it is currently targeted in the clinical practice for liver disease such as primary cholangitis. At a variance of FXR activation, native FGF19 has strong anti-cholestatic and anti-fibrotic activity in the liver but it retains peculiar pro-tumorigenic actions. Thus, novel analogues have been generated to avoid tumorigenic capacity while maintaining BA metabolic action. Here we present a novel and intriguing view on the putative possibility to target the FXR-FGF19 duo in order to offer a bona fide promising therapeutic approach to bile acid promoted hepatocarcinoma.


Termination of early gestation with a vaginal polysiloxane device impregnated with (15S)-15 methyl prostaglandin F2alpha methylester.
An investigation of the abortifacient activity of (15S)-15 methyl prostaglandin F2alpha methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the device prior to its scheduled removal.


Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy.
Recent data suggest that prenatal stress negatively affects pregnancy and infant outcome. Existing studies implicate dysregulation of the immune and endocrine systems in stress-related increases in premature labor and poor birth outcome, but no published studies have directly addressed the relationships among these variables during pregnancy. We sought to test the hypothesis that high levels of psychosocial stress and low levels of social support during pregnancy alter maternal cytokine profiles in a manner that contributes to poor birth outcomes. Psychosocial stress and social support were measured in 24 women with overtly normal pregnancies once during each trimester of pregnancy. Levels of interleukin-10 (IL-10), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were assessed concurrently with stress and support measurements. High social support was associated with low stress scores. Elevated stress scores were positively correlated with higher levels of the proinflammatory cytokines IL-6 and TNF-alpha, and with low levels of the antiinflammatory cytokine IL-10. These findings provide initial support for our hypothesis that stress-related neural immune interactions may contribute to pregnancy complications and poor outcome, but require further study to determine the mechanism and significance of these effects.


Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies.
Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed.


Effects of hemopoietic growth factors on stem cells in vitro.
The central feature of hemopoiesis is the lifelong, stable cell renewal. This process is supported by hemopoietic stem cells, which in the steady-state appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as IL-1, IL-6, and G-CSF. Available evidence indicates that the effects of IL-1 on stem cells are indirectly mediated in part by IL-6 and G-CSF. Once the stem cells leave G0 and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. While several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a stochastic (random) process. The proliferation of early hemopoietic progenitors appears to be supported by IL-3, IL-4, and/or GM-CSF. Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as Ep (for erythropoiesis), G-CSF (for neutrophil production), and IL-5 (for eosinophilopoiesis). Thus, hemopoietic proliferation appears to be regulated by a cascade of factors directed at different developmental stages.


Multiple amino acids in the glycoprotein of rabies virus are responsible for pathogenicity in adult mice.
We have reported that the region between amino acids 164 and 303 in the glycoprotein of rabies Nishigahara strain is important for lethality in adult mice. The region contains nine amino acid substitutions between the virulent Nishigahara and the avirulent RC-HL strains. In order to determine key residues for the pathogenicity, two chimeric strains and seven mutants were generated and examined for pathogenicities. The R(G 242/255/268) strain, in which amino acids at positions 242, 255, and 268 were replaced by those from the Nishigahara strain in the genomic backbone of the RC-HL strain, showed the same lethality as that of the Nishigahara strain in mice. Mutants in which one or two of these three amino acids were replaced by those from the Nishigahara strain did not revert to the lethality of the R(G 242/255/268) strain. These results demonstrate that at least these three amino acids are related to enhancement of pathogenicity. It is thought that multiple amino acids of the G protein are related to the pathogenicity of rabies viruses.


Cost analysis from two randomized trials of sirolimus-eluting stents versus paclitaxel-eluting stents in high-risk patients with coronary artery disease.
This study sought to analyze the cost of percutaneous coronary interventions with use of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) in patients at high risk of restenosis. Recent studies have shown different clinical efficacy with these drug-eluting stents. Whether this difference extends on cost estimates between the 2 stents is not known. We included 450 patients with diabetes mellitus and in-stent restenosis from 2 randomized studies comparing SES with PES. Assigned costs for the economic evaluation were the initial hospitalization and all subsequent cardiac-related inpatient/outpatient health resources during 9 to 12 months of clinical follow-up. The economic evaluation was performed from the health insurance system's perspective. There were no differences between the 2 study groups regarding mortality (p = 0.78) and myocardial infarction rates (p = 0.76). Target lesion revascularization was performed in 16 patients (7.1%) in the SES group and in 34 patients (15.1%) in the PES group (p = 0.01). Initial hospital costs were not significantly different between the 2 stents (p = 0.53). The follow-up costs were, however, different: 2,684 +/- 2,072 euros per patient treated with SES and 4,527 +/- 6,466 euros per patient treated with PES (p < 0.001). Total costs also differed at the end of the follow-up: 8,924 +/- 3,077 euros per patient treated with SES and 10,903 +/- 7,205 euros per patient treated with PES (p < 0.001). In patients at high risk of restenosis, use of SES is associated with lower costs compared with PES. The cost savings are mainly due to the reduced need of repeat revascularization procedures with SES.


Cerebral palsy.
Cerebral palsy (CP) is the leading cause of childhood disability. This article reviews common presentations of CP and its possible causes. The management of common problems seen in affected children is discussed in a system-based approach. Many treatment options are available for CP, with varying degrees of evidence and acceptance. As individuals who have CP transition into adulthood, they face unique issues that are not well recognized in the medical community. This article briefly reviews the psychosocial impact of this chronic disease on individuals and their caregivers and family.


Episodic memory in adults with autistic spectrum disorders: recall for self- versus other-experienced events.
People with autistic spectrum disorders (ASD) have difficulties in recalling recently experienced events, which is dependent upon intact functioning of several aspects of 'self awareness'. The current study examined impaired episodic recall in ASD and its relationship to specific impairments in aspects of 'self awareness'. Between-group (participants with learning disabilities with and without autistic spectrum disorder) experimental design examining free and cued recall of table-top activities that were either self-experienced by participants or observed being performed by the experimenter. Participants with ASD did not show superiority of free recall for self-experienced events over observed events, nor for recall of other-experienced events over self-experienced events, but did demonstrate a superiority for cued recall of self-experienced events. The implications for theory and practice are discussed.


Intensity-invariant nonlinear filtering for detection in camouflage.
We introduce a method based on an orthonormal vector space basis representation to detect camouflaged targets in natural environments. The method is intensity invariant so that camouflaged targets are detected independently of the illumination conditions. The detection technique does not require one to know the exact camouflage pattern, but only the class of patterns (e.g., foliage, netting, woods). We use nonlinear filtering and the calculation of several correlations. The nonlinearity of the filtering process also allows high discrimination against false targets. Several experiments confirm the target detectability where strong camouflage might delude even human viewers.


Calcium scoring on coronary computed angiography tomography with photon-counting detector technology: Predictors of performance.
Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy. CCTA datasets were acquired with either 120 or 140 kVp. CAC scores and volumes were calculated from TNC and VNI images in 197 consecutive patients undergoing CCTA. CAC density score, mean volume/lesion, aortic Hounsfield units and standard deviations were then measured. Finally, percentage deviation (VNI - TNC/TNC∗100) of CTA-derived CAC scores from non-enhanced scans was calculated for each patient. Predictors (including anthropometric and acquisition parameters, as well as CAC characteristics) of the degree of discrepancy were evaluated using linear regression analysis. While the agreement between TNC and VNI was substantial (mean bias, 6.6; limits of agreement, 178.5/145.3), a non-negligible proportion of patients (36/197, 18.3%) were falsely reclassified as CAC score = 0 on VNI. The use of higher tube voltage significantly decreased the percentage deviation relative to TNC-based values (β = -0.21 [95%CI: 0.38 to -0.03], p = 0.020) and a higher CAC density score also proved to be an independent predictor of a smaller difference (β = -0.22 [95%CI: 0.37 to -0.07], p = 0.006). The performance of VNI-based calcium scoring may be improved by increased tube voltage protocols, while the accuracy may be compromised for calcified lesions of lower density. The implementation of VNI in clinical routine, however, needs to be preceded by a solution for detecting smaller lesions as well.


Pentobarbital intoxication as a potential underlying cause for electrocution in a bearded vulture.
A bearded vulture (Gypaetus barbatus) found dead in northern Spain presented external lesions consistent with electrocution as the cause of death. During forensic examination, macroscopic lesions suggested potential comorbidity, so samples were collected for molecular and toxicological analyses. Gastric content and liver were analysed for toxic substances, and pentobarbital (a common pharmaceutical used for euthanasia in domestic animals) was detected at a concentration of 37.3 and 0.05 µg/g, respectively. Other toxicological, viral and endoparasite analyses (avian malaria, avian influenza and flaviviruses) were negative. Thus, although the cause of death was electrocution, pentobarbital intoxication likely impaired the equilibrium and reflexes of the individual, possibly causing the bird to contact energized wires that it would not have otherwise. These results underline the importance of comprehensive analysis of forensic cases of wildlife deaths and reveal barbiturate poisoning as an additional threat for the conservation of the bearded vulture in Europe.


Coaching and leadership for the diffusion of innovation in health care: a different type of multi-organization improvement collaborative.
Health care organizations have suffered a steady decrease in operating margins in recent years while facing increased competition and pressure to provide ever-higher levels of customer service, quality of care, and innovation in delivery methodologies. The ability to rapidly find and implement changes that will lead to strategic improvement is critical. To assist member organizations in dealing with these issues, VHA Upper Midwest launched the Coaching and Leadership Initiative (VHA-CLI) in January 1999. The initiative was intended to develop new methods of collaborating for organizational learning of best practices, with a focus on generalizable change and deliberate leadership supports for deployment, diffusion, and sustainability. The emphasis was on the spread of ideas for improvement into all relevant corners of the organization. The structure of the VHA-CLI collaborative involved four waves of demonstration teams during 2 years. Each meeting of the collaborative included an executive session, team learning sessions (concepts applied to their improvement projects), and planning for the 6-month action period following the meeting. An important feature of the collaborative is the way in which teams in the various waves overlapped. For example, the Wave 1 team for a given organization came to a learning session in January 1999. At the second collaborative meeting in June 1999, the Wave 1 teams reported on the progress in their pilot sites. This meeting was also the kick-off session for the Wave 2 teams, which could learn about organizational culture and the improvement model from the efforts of their colleagues on Wave 1. Wave 1 teams also learned about and planned for spreading their efforts to other sites beyond the pilot. The pattern of multiple teams stretching across two waves of activity was repeated at every meeting of the collaborative. Each organization in the collaborative has achieved improved outcomes around its selected clinical topics. In total, 26 teams have made significant improvement in 17 different topic areas. In addition, each organization has been able to successfully spread tested improvements to other individuals, teams, or locations, and the improvement work has become easier and more rapid with each successive cycle. The learning process initiated by this project will continue for at least another year in the VHA Upper Midwest region and will be expanded as participating organizations in other regions enroll in the VHA's national effort.


["How this conflict tortures me!" The man Emil Kraepelin as viewed in his poems].
In 1928, Emil Kraepelin's poems were published posthumously. They provide thus far unknown insight into his intellectual and emotional world. Here we meet the man Kraepelin rather than the psychiatrist. We feel the rather pensive mood he expresses using the same allegories from the world of nature again and again. Kraepelin suffers from the fate of his mother country and his profession as a doctor, which puts him in "slave chains," thus preventing him from following his own course and fulfilling his longings. Those can be seen in his wish to dedicate himself fully to his nosological, psychopathological, or experimental psychological research. One wonders why he did not push his aims through more forcefully in these areas. Procrastination became Kraepelin's self-deception, since he could enter those worlds periodically only. In this way, they resemble his journeys to the south, which became a metaphor for freedom.


Evaluation of alloreactive T cells based on the degree of MHC incompatibility using flow cytometric mixed lymphocyte reaction assay in dogs.
It has become anticipated that regenerative medicine will extend into the field of veterinary medicine as new treatments for various disorders. Although the use of allogeneic stem cells for tissue regeneration is more attractive than that of autologous cells in emergencies, the therapeutic potential of allogeneic transplantation is often limited by allo-immune responses inducing graft rejection. Therefore, a methodology for quantifying and monitoring alloreactive T cells is necessary for evaluating allo-immune responses. The mixed lymphocyte reaction (MLR) is widely used to evaluate T cell alloreactivity. In human, flow cytometric MLR with carboxyfluorescein diacetate succinimidyl ester has been established and used as a more useful assay than conventional MLR with radioisotope labeling. However, the available information about alloreactivity based on the differences of dog major histocompatibility complex (MHC) (dog leukocyte antigen, DLA) is quite limited in dog. In this paper, we describe our established flow cytometric MLR method that can quantify the T cell alloreactivity while distinguishing cell phenotypes in dog, and T cell alloreactivity among DLA-type matched pairs was significantly lower than DLA-mismatched pairs, suggesting that our developed flow cytometric MLR method is useful for quantifying T cell alloreactivity. In addition, we demonstrated the advantage of DLA homozygous cells as a donor (stimulator) for allogeneic transplantation. We also elucidated that the frequency of alloreactive T cell precursors was almost the same as that of mouse and human (1-10%). To our knowledge, this is the first report to focus on the degree of allo-immune responses in dog based on the differences of DLA polymorphisms.


Analysis of steroids. XXXVIII. The use of high-performance liquid chromatography with diode-array UV detection for estimating impurity profiles of steroid drugs.
High-performance liquid chromatography (HPLC) diode-array UV-spectrophotometric detection is used for estimating impurity profiles of steroid drugs. It is shown to be a very useful first screening method for the identification of UV-active impurities and degradation products, giving a rapid answer to many questions or at least providing important initial information to complement the results obtained by other spectroscopic techniques. In this paper the estimation of the impurity profiles of ethynyloestradiol, norgestrel, and norethisterone, and of the degradation product of RGH-1113 (3-chloro-, 6,9-difluoro-11 beta,16 alpha,17 alpha,21-tetrahydroxy-1,3,5-pregnatrien-20-one 16,17-acetonide 21-acetate) will be discussed.


National Diagnostic Reference Levels for Endovascular Aneurysm Repair and Optimisation Strategies.
The International Commission on Radiological Protection (ICRP) has highlighted the large number of medical specialties using fluoroscopy outside imaging departments without programmes of radiation protection (RP) for patients and staff. Vascular surgery is one of these specialties and endovascular aneurysm repair (EVAR) is one of the most challenging procedures requiring RP guidance and optimisation actions. The recent European Directive on Basic Safety Standards requires the use and regular update of diagnostic reference levels (DRL) for interventional procedures. The objective of the study was to know the doses of patients undergoing EVAR with mobile Xray systems and with hybrid rooms (fixed Xray systems), to obtain national DRLs and suggest optimisation actions. The Spanish Chapter of Endovascular Surgery launched a national survey that involved hospitals for 10 autonomous communities representing the 77% of the Spanish population (46.7 million inhabitants). Patient dose values from mobile Xray systems were available from nine hospitals (sample of 165 EVAR procedures) and data from hybrid rooms, from seven hospitals, with dosimetric data from 123 procedures. The initial national DRLs have been obtained, as the third quartile of the median values from the different centres involved in the survey. The proposed national DRLs are 278 Gy cm2 for hybrid rooms and 87 Gy cm2 for mobile Xray systems, and for cumulative air kerma (cumulative AK) at the patient entrance reference point, 1403 mGy for hybrid rooms, and 292 mGy for mobile systems. An audit of patient doses for EVAR procedures to identify optimised imaging protocol strategies is needed. It is also appropriate to evaluate the diagnostic information required for EVAR procedures. The increase by a factor of 3.2 (for kerma area product) and 4.8 (for cumulative AK) in the DRLs needs to be justified when the procedures are performed in the hybrid rooms rather than with mobile Xray systems.