Subject(s)
Aortic Valve Stenosis , Animals , Aortic Valve , Aortic Valve Stenosis/etiology , Mice , Treatment OutcomeABSTRACT
Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.
ABSTRACT
Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.
ABSTRACT
BACKGROUND: Radial artery access is the primary approach for coronary interventions due to higher safety profile in comparison to femoral access. Radial artery occlusion (RAO) is the main complication of transradial catheterization that can lead to severe symptoms and a permanent artery occlusion. The incidence of RAO after transradial access ranges from 5 to 38% and data regarding treatment is scarce. Whether anticoagulation and vasoactive medication provides an additional benefit in recovery of radial artery patency (RAP) after catheterization has not been investigated in detail. AIM: The objective was to investigate the impact of anticoagulation and vasoactive medication on regained patency after documented RAO following transradial catheterization. PATIENTS AND METHODS: Overall 2635 patients were screened. 2215 (84%) catheterizations were performed by femoral and 420 (16%) by radial access. In 30 patients RAO was observed. In case of RAO patients were classified in three groups: Anticoagulation, anticoagulation added with alprostadil and controls. Follow-up was conducted after 3 months with ultrasound and clinical examination. RESULTS: Eight patients received anticoagulation and 11 patients anticoagulation together with alprostadil. Eleven patients served as controls. Recovery of RAP after catheterization was higher following either treatment (79.5%) compared to controls (0%, p = 0.006). Subgroup analysis yielded a higher RAP recovery in patients treated with anticoagulation (62.5%) as compared to controls (0%, p = 0.002). No effect on regained RAP was found with additional alprostadil therapy (33.3%) compared to anticoagulation therapy (62.5%, p = 0.229). CONCLUSION: RAO should be treated with anticoagulation to regain patency. Addition of vasoactive medication does not lead to further beneficial effects. Further research is needed regarding preventive and therapeutic strategies following RAO.
Subject(s)
Alprostadil/therapeutic use , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/prevention & control , Cardiac Catheterization/adverse effects , Radial Artery/drug effects , Vasodilator Agents/therapeutic use , Adult , Aged , Arterial Occlusive Diseases/epidemiology , Arterial Occlusive Diseases/etiology , Cardiac Catheterization/methods , Case-Control Studies , Female , Humans , Incidence , Male , Middle Aged , Radial Artery/pathology , Radial Artery/surgeryABSTRACT
OBJECTIVES: The objective of this study is to evaluate the effect of short-term changes in the oral microbial ecology of dental plaque and plaque levels after topical treatment of a combination of 10% povidone iodine (PI) and 5% sodium fluoride varnish (FV). MATERIALS AND METHODS: A single group design intervention study on 12 pediatric patients, who underwent two baseline plaques samplings before the intervention, were enrolled in the study. A modified mixed dentition Silness-Löe plaque index score was used to assess plaque accumulation and microbial composition was assessed by amplicon sequencing analysis of the 16S rRNA V4 region. RESULTS: Dental plaque accumulation (P = 0.0424) was reduced after 1 week using PI/FV application. This reduction was not observed between the two double-baseline visits. 16S rRNA analysis showed that the single PI/FV therapy did not have dramatic shifts in the plaque microbiome community depicted by hierarchical cluster and principle component analysis. More subtle changes were found when analyzing the Shannon diversity index after the application of PI/FV vs two baselines prior to combination therapy. CONCLUSIONS: The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity but reduced biofilm accumulation following PI/FV therapy. Repeated uses of PI/FV may augment plaque control during dental rehabilitation in children.
Subject(s)
Anti-Infective Agents, Local/therapeutic use , Biofilms/drug effects , Dental Plaque/microbiology , Microbiota/drug effects , Povidone-Iodine/therapeutic use , Sodium Fluoride/therapeutic use , Cariostatic Agents , Child , Dental Plaque/prevention & control , Dental Plaque Index , Drug Combinations , HumansABSTRACT
Due to the spread of intervertebral disc degeneration, insurance companies and experts are regularly confronted with related assessments of insured persons under their private accident insurance. These claims pose a particular challenge for experts, since, in addition to the clinical assessment of the facts, extensive knowledge of general accident insurance conditions, case law and current study findings is required. Each case can only be properly assessed through simultaneous consideration of both the medical and legal facts. These guidelines serve as the basis for experts and claims.managers with respect to the appropriate individual factual assessment of intervertebral disc degeneration in private accident insurance.
Subject(s)
Disability Evaluation , Expert Testimony/legislation & jurisprudence , Insurance Claim Review/legislation & jurisprudence , Insurance, Accident/legislation & jurisprudence , Intervertebral Disc Degeneration/diagnosis , Intervertebral Disc Degeneration/therapy , Expert Testimony/economics , Expert Testimony/methods , Germany , Humans , Insurance Claim Review/economics , Insurance, Accident/economics , Intervertebral Disc Degeneration/economicsABSTRACT
AIM: To assess intervendor agreement of cardiovascular magnetic resonance feature tracking (CMR-FT) and to study the impact of repeated measures on reproducibility. MATERIALS AND METHODS: Ten healthy volunteers underwent cine imaging in short-axis orientation at rest and with dobutamine stimulation (10 and 20 µg/kg/min). All images were analysed three times using two types of software (TomTec, Unterschleissheim, Germany and Circle, cvi(42), Calgary, Canada) to assess global left ventricular circumferential (Ecc) and radial (Err) strains and torsion. Differences in intra- and interobserver variability within and between software types were assessed based on single and averaged measurements (two and three repetitions with subsequent averaging of results, respectively) as determined by Bland-Altman analysis, intraclass correlation coefficients (ICC), and coefficient of variation (CoV). RESULTS: Myocardial strains and torsion significantly increased on dobutamine stimulation with both types of software (p<0.05). Resting Ecc and torsion as well as Ecc values during dobutamine stimulation were lower measured with Circle (p<0.05). Intra- and interobserver variability between software types was lowest for Ecc (ICC 0.81 [0.63-0.91], 0.87 [0.72-0.94] and CoV 12.47% and 14.3%, respectively) irrespective of the number of analysis repetitions. Err and torsion showed higher variability that markedly improved for torsion with repeated analyses and to a lesser extent for Err. On an intravendor level TomTec showed better reproducibility for Ecc and torsion and Circle for Err. CONCLUSIONS: CMR-FT strain and torsion measurements are subject to considerable intervendor variability, which can be reduced using three analysis repetitions. For both vendors, Ecc qualifies as the most robust parameter with the best agreement, albeit lower Ecc values obtained using Circle, and warrants further investigation of incremental clinical merit.
Subject(s)
Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging, Cine/methods , Software , Adult , Cardiotonic Agents , Dobutamine , Female , Healthy Volunteers , Humans , Male , Middle Aged , Reproducibility of ResultsABSTRACT
AIM: To evaluate the potential of real-time phase-contrast flow magnetic resonance imaging (MRI) at 40 ms resolution for the simultaneous determination of blood flow in the ascending aorta (AA) and superior vena cava (SVC) in response to reduced intrathoracic pressure (Mueller manoeuvre). MATERIALS AND METHODS: Through-plane flow was assessed in 20 healthy young subjects using real-time phase-contrast MRI based on highly undersampled radial fast low-angle shot (FLASH) with image reconstruction by regularized non-linear inversion. Haemodynamic alterations (three repetitions per subject = 60 events) were evaluated during normal breathing (10 s), inhalation with nearly closed epiglottis (10 s), and recovery (20 s). RESULTS: Relative to normal breathing and despite interindividual differences, reduced intrathoracic pressure by at least 30 mmHg significantly decreased the initial peak mean velocity (averaged across the lumen) in the AA by -24 ± 9% and increased the velocity in the SVC by +28 ± 25% (p < 0.0001, n = 23 successful events). Respective changes in flow volume per heartbeat were -25 ± 9% in the AA and +49 ± 44% in the SVC (p < 0.0001, n = 23). Flow parameters returned to baseline during sustained pressure reduction, while the heart rate was elevated by 10% (p < 0.0001) after the start (n = 24) and end (n = 17) of the manoeuvre. CONCLUSIONS: Real-time flow MRI during low intrathoracic pressure non-invasively revealed quantitative haemodynamic adjustments in both the AA and SVC.
Subject(s)
Aorta/physiology , Hemodynamics/physiology , Magnetic Resonance Imaging/methods , Pulmonary Circulation/physiology , Respiratory Mechanics/physiology , Vena Cava, Superior/physiology , Adult , Analysis of Variance , Blood Flow Velocity/physiology , Blood Pressure/physiology , Female , Heart Rate/physiology , Humans , Image Processing, Computer-Assisted/methods , Inhalation/physiology , Male , Reference Values , Stroke Volume/physiologyABSTRACT
Spinal metastases invariably affect the majority of patients with cancer. Many will develop symptoms related to pain and disability from epidural spinal cord compression as well as pathologic fracture of the vertebrae. With the emergence of targeted systemic therapies and a better understanding of cancer biology, patients are living longer with bony metastases. This poses particular challenges, as palliation of pain and maintenance of local tumor control are paramount to quality of life and overall functional independence for these patients. Stereotactic radiosurgery (SRS) has emerged as a potent primary standalone and adjuvant treatment option for spinal metastases. To date, the primary indications for SRS include 1) upfront standalone treatment for painful bony metastases in the oligometastatic patient, 2) standalone or post-operative treatment following progression or recurrence of local disease despite previous conventional external beam radiation therapy (cEBRT), and 3) following surgery during which epidural disease is decompressed and the spine stabilized when indicated. SRS has demonstrated a significant advantage over cEBRT for tumors traditionally regarded as relatively radioresistant such as sarcoma, melanoma, renal cell carcinoma, non-small cell lung cancer and colon carcinoma.9 The radiobiological advantage of increased tumoricidal dose delivery and spinal cord dose sparing in SRS have made this a powerful treatment alternative to cEBRT particularly within the context of re-irradiation. Given the limitations of spinal cord dose constraints, surgery is still the first-line therapy in patients with high-grade epidural spinal cord compression (ESCC). Epidural compression can be treated with SRS, however this risks radiation-induced myelopathy and challenges the safety of effective dose delivery at the dural margin.11 With increasing dose, radiation-induced vertebral fracture is the most serious and prevalent side effect of SRS.53 An overview of SRS, including the most common indications, complications, and outcomes for spinal metastases are presented here.
Subject(s)
Radiosurgery , Spinal Neoplasms/surgery , Combined Modality Therapy/methods , Humans , Neoplasm Recurrence, Local/surgery , Radiosurgery/methods , Spinal Cord Compression/surgery , Spinal Neoplasms/secondary , Treatment OutcomeABSTRACT
"Communicative psychotherapy" was developed in the 1960s by the East German psychotherapist and psychiatrist Christa Kohler (1928-2004) for the treatment of "neuroses". Similar to established present-day psychotherapeutic methods, such as cognitive behaviour therapy, it combined diverse therapeutic approaches into an integrated treatment programme. This included individual and group therapy, exercise, work and occupational therapy. In contrast to modern psychotherapeutic practice, communicative psychotherapy was based on a firm system of values, namely socialist ideals. According to this system, psychological breakdown was viewed and treated ideologically. In addition, any lack of conformity with the East German system was likewise regarded as a psychopathological deviation, which should be subjected to psychological treatment. The latter concept requires a critical analysis from a current-day perspective. For the first time, this paper concentrates on Kohler's work on neuroses and the theory and practice of her communicative psychotherapy, albeit without neglecting Kohler's other scientific works, her biographical information and her Stasi documents.
Subject(s)
Psychiatry/history , Psychotherapy/history , Cognitive Behavioral Therapy , Combined Modality Therapy , Communication , Germany , Germany, East , History, 20th Century , Humans , Music Therapy , Neurotic Disorders/diagnosis , Neurotic Disorders/psychology , Neurotic Disorders/therapy , Occupational Therapy , Psychotherapy, Group , SocialismABSTRACT
Virtually all massive galaxies, including our own, host central black holes ranging in mass from millions to billions of solar masses. The growth of these black holes releases vast amounts of energy that powers quasars and other weaker active galactic nuclei. A tiny fraction of this energy, if absorbed by the host galaxy, could halt star formation by heating and ejecting ambient gas. A central question in galaxy evolution is the degree to which this process has caused the decline of star formation in large elliptical galaxies, which typically have little cold gas and few young stars, unlike spiral galaxies.
ABSTRACT
Arterial hypertension leads to cardiac restructuring and damage. This "hypertensive heart disease" includes left ventricular hypertrophy. In addition, it is also considered responsible for diastolic and systolic dysfunction, vascular manifestations of microangiopathy and in a broader sense also coronary heart disease as well as cardiac dysrhythmias and sudden cardiac death. The pathophysiological mechanisms depend on a complex neurohumoral regulation and the ensuing change in cardiac structure and output. The initial compensation for increased cardiac demand is followed by permanent heart damage and successive decompensation. At this point the typical complaints involved in cardiac insufficiency or ischemia become evident. Determining the diagnosis is particularly important early on since the prognosis with regard to morbidity and mortality deteriorates if the hypertensive condition persists and the heart develops lasting damage.
Subject(s)
Hypertension/complications , Hypertension/physiopathology , Models, Cardiovascular , Myocardial Ischemia/etiology , Myocardial Ischemia/physiopathology , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , HumansABSTRACT
The Hartree-Fock method, two common density functionals (PBE and B3LYP), and two new functionals (B97-D and B2PLYP) together with very large AO basis sets are used to compute the isomerization energies for substituted (R [Formula: see text] H, F, Cl) branched to linear alkanes and silanes. The results of accurate SCS-MP2 computations are taken as reference. These reactions are an important test of how nonlocal electron correlation effects on medium-range lengths scales in saturated molecules are treated by approximate quantum chemical methods. It is found that the unacceptably large errors observed previously for hydrocarbons persist also for the here considered more polar systems. Although the B97-D and B2PLYP functionals provide improved energetics, the problem is not fully solved, and thus these systems are suggested as mandatory benchmarks for future density functionals.
ABSTRACT
The primate posterior parietal cortex (PPC) plays an important role in representing and recalling spatial relationships and in the ability to orient visual attention. This is evidenced by the parietal activation observed in brain imaging experiments performed during visuo- spatial tasks, and by the contralateral neglect syndrome that often accompanies parietal lesions. Individual neurons in monkey parietal cortex respond vigorously to the appearance of single, behaviorally relevant stimuli, but little is known about how they respond to more complex visual displays. The current experiments addressed this issue by recording activity from single neurons in area 7a of the PPC in monkeys performing a spatial version of a match-to-sample task. The task required them to locate salient stimuli in multiple-stimulus displays and release a lever after a subsequent stimulus appeared at the same location. Neurons responded preferentially to the appearance of salient stimuli inside their receptive fields. The presence of multiple stimuli did not affect appreciably the spatial tuning of responses in the majority of neurons or the population code for the location of the salient stimulus. Responses to salient stimuli could be distinguished from background stimuli approximately 100 ms after the onset of the cue. These results suggest that area 7a neurons represent the location of the stimulus attracting the animal's attention and can provide the spatial information required for directing attention to a salient stimulus in a complex scene.
Subject(s)
Attention/physiology , Neurons/physiology , Parietal Lobe/physiology , Space Perception/physiology , Animals , Color Perception/physiology , Electrophysiology , Macaca mulatta , Male , Orientation/physiology , Parietal Lobe/cytology , Photic StimulationABSTRACT
Everyday visual scenes contain a variety of stimuli that vary in their significance. The companion paper demonstrates that neurons in the posterior parietal cortex (PPC) are capable of encoding the spatial locations of the salient stimulus in multiple stimulus scenes. The present experiment sought to address how neuronal responses to stimuli appearing in the receptive field are modulated after attention has been drawn to one of multiple stimuli in a visual scene. We recorded from area 7a of the PPC in monkeys trained to do a spatial version of a match-to-sample task. The results show that neuronal responses are greatly suppressed when stimuli appear at previously attended locations. No reduction in responsiveness is observed for locations where stimuli had previously appeared but did not draw attention. These results support the hypothesis that area 7a has a role in redirecting attention to stimuli appearing at novel, unattended locations.
Subject(s)
Attention/physiology , Neurons/physiology , Parietal Lobe/physiology , Space Perception/physiology , Animals , Macaca mulatta , Male , Orientation/physiology , Parietal Lobe/cytology , Photic StimulationABSTRACT
Protein phosphorylation represents a ubiquitous control mechanism in living cells. The structural prerequisites and consequences of this important post-translational modification, however, are poorly understood. Oncoprotein 18/stathmin (Op18) is a globally disordered phosphoprotein that is involved in the regulation of the microtubule (MT) filament system. Here we document that phosphorylation of Ser63, which is located within a helix initiation site in Op18, disrupts the transiently formed amphipathic helix. The phosphoryl group reduces tubulin binding 10-fold and suppresses the MT polymerization inhibition activity of Op18's C-terminal domain. Op18 represents an example where phosphorylation occurs within a regular secondary structural element. Together, our findings have implications for the prediction of phosphorylation sites and give insights into the molecular behavior of a globally disordered protein.
Subject(s)
Microtubule Proteins , Phosphoproteins/chemistry , Tubulin/chemistry , Circular Dichroism , Dose-Response Relationship, Drug , Humans , Hydrogen-Ion Concentration , Ions , Magnetic Resonance Spectroscopy , Microtubules/chemistry , Models, Molecular , Phosphoproteins/metabolism , Phosphorylation , Protein Binding , Protein Conformation , Protein Structure, Secondary , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Stathmin , Surface Plasmon Resonance , Temperature , Tubulin/metabolismABSTRACT
In protein interaction analysis, one promising method to identify the involved proteins and to characterize interacting sites at the same time is the mass spectrometric analysis of enzymatic hydrolysates of covalently cross-linked complexes. While protein identification can be accomplished by the methodology developed for proteome analysis, the unequivocal detection and characterization of cross-linked sites remained involved without selection criteria for linked peptides in addition to mass. To provide such criteria, we incorporated cross-links with a distinct isotope pattern into the microtubule-destabilizing protein Op18/stathmin (Op18) and into complexes formed by Op18 with tubulin. The deuterium-labeled cross-linking reagents bis(sulfosuccinimidyl)-glutarate-d4, -pimelate-d4, and -sebacate-d4 were prepared together with their undeuterated counterparts and applied as a 1:1 mixture of the respective d0 and d4 isotopomers. The resulting d0/d4 isotope tags allowed a straightforward mass spectrometric detection of peptides carrying the linker even in complex enzymatic protein hydrolysates. In the structure elucidation of the linked peptides by MS/MS, the assignment of the linked amino acids was again greatly facilitated by the d0/d4 tag. By applying two cross-linkers with similar reactivity but different spacer length in parallel, even doublets with very low intensity could be assigned with high confidence in MS and MS/MS spectra. Since in the Op18-tubulin complexes only a limited number of peptides carried the linker, the identification of the involved proteins per se was not impeded, thus accomplishing both protein identification and characterization of interacting sites in the same experiment. This novel methodology allowed us to significantly refine the current view of the complex between Op18 and tubulin corroborating the tubulin "capping" activity of the N-terminal domain of Op18.
Subject(s)
Cross-Linking Reagents/chemistry , Decanoic Acids/chemistry , Glutarates/chemistry , Microtubule Proteins , Pimelic Acids/chemistry , Proteins/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Succinimides/chemistry , Amino Acid Sequence , Cross-Linking Reagents/chemical synthesis , Decanoic Acids/chemical synthesis , Deuterium , Glutarates/chemical synthesis , Humans , Hydrolysis , Isotope Labeling , Microscopy, Electron , Molecular Sequence Data , Molecular Structure , Peptides/chemistry , Phosphoproteins/chemistry , Pimelic Acids/chemical synthesis , Protein Conformation , Proteome/analysis , Stathmin , Succinimides/chemical synthesis , Trypsin/metabolism , Tubulin/chemistry , Tubulin/ultrastructureABSTRACT
We previously reported that a helical trigger segment within the GCN4 leucine zipper monomer is indispensable for the formation of its parallel two-stranded coiled coil. Here, we demonstrate that the intrinsic secondary structure of the trigger site is largely stabilized by an intrahelical salt bridge. Removal of this surface salt bridge by a single amino acid mutation induced only minor changes in the backbone structure of the GCN4 leucine zipper dimer as verified by nuclear magnetic resonance. The mutation, however, substantially destabilized the dimeric structure. These findings support the proposed hierarchic folding mechanism of the GCN4 coiled coil in which local helix formation within the trigger segment precedes dimerization.