Pre-emptive analgesic efficacy of the non-steroidal anti-inflammatory drug, diclofenac sodium, was tested in 21 young, fit, patients undergoing third molar extractions in a double-blind, randomised, ...cross-over, trial. Pain scores and mouth opening were observed for 1 week after the operation and these did not show any differences following pre- and postoperative oral administration of diclofenac sodium 100 mg (
P > 0.05). There were no differences in the patients' preference for the two methods of treatment (
P > 0.05). The study suggests that the non-steroidal anti-inflammatory drug diclofenac sodium does not cause any significant pre-emptive analgesic effects in the dose administered.
Background Use of one or more arterial grafts to revascularize two-vessel and three-vessel coronary artery disease has been shown to improve coronary artery bypass graft surgery (CABG) survival. Yet, ...the presumed long-term survival benefits of all-arterial CABG have not been quantified. Methods We compared propensity-adjusted 12-year survival in two contemporaneous multivessel primary CABG cohorts with all patients receiving 2 or more grafts: (1) all-arterial cohort (n = 612; 297 three-vessel disease 49%); and (2) single internal thoracic artery (ITA) plus saphenous vein (SV) cohort (n = 4,131; 3,187 three-vessel disease 77%). Results Early (30-day) deaths were similar for the all-arterial and ITA/SV cohorts (8 1.30% versus 69 1.67%) whereas late mortality was substantially greater for the ITA/SV cohort (85 13.9% versus 1,216 29.4%; p < 0.0001). The risk-adjusted 12-year survival was significantly better for all-arterial (with a risk ratio RR = 0.60; 95% confidence interval CI: 0.48 to 0.75; p < 0.001), but this benefit was true only for three-vessel disease (RR = 0.58; 95% CI: 0.43 to 0.78; p < 0.001) and not for two-vessel disease (RR = 0.97; 95% CI: 0.66 to 1.43; p = 0.89). The all-arterial survival benefit was also true for varying risk subcohorts: no diabetes mellitus (RR = 0.50; 95% CI: 0.37 to 0.69), diabetes mellitus (RR = 0.77; 95% CI: 0.56 to 1.07), ejection fraction 40% or greater (RR = 0.60; 95% CI: 0.45 to 0.78), and ejection fraction less than 40% (RR = 0.62; 95% CI: 0.40 to 0.98). Lastly, the multivariate analysis indicated a strong long-term effect of completeness of revascularization, particularly for all-arterial patients, so that compared with patients with two grafts, survival was significantly better when three grafts (RR = 0.54; 95% CI: 0.33 to 0.87) or four grafts (RR = 0.40; 95% CI: 0.21 to 0.76) were completed. Conclusions All-arterial revascularization is associated with significantly better 12-year survival compared with the standard single ITA with saphenous vein CABG operation, in particular for triple-vessel disease patients. The completeness of revascularization of the underlying coronary disease is critical for maximizing the long-term benefits of arterial-only grafting.
The synthesis of stable RNA in bacteria is known to be regulated by a stringent control mechanism. Characteristic of stringent‐regulated promoters, all ribosomal RNA promoters P1, but not P2, contain ...a GC‐rich discriminator sequence assumed to be important for such a control. Using site‐directed mutagenesis we have altered both the rrnB P2 and the synthetic tac promoter to the consensus GCGC discriminator motif. The modified promoters were placed upstream of the structural gene encoding the chloramphenicol acetyltransferase. The response of the modified promoters to amino acid starvation, changes in the growth rate or differences in the basal level of guanosine tetraphosphate (ppGpp) were determined in vivo. The results clearly show, that the discriminator motif is sufficient to convert the ribosomal RNA promoter P2 to a stringent, as well as growth‐rate regulated, promoter. By contrast, the same discriminator sequence linked to the synthetic tac promoter does not convert this promoter to either stringency or growth‐rate regulation. Finally, the results presented in this study reinforce the view that stringent and growth‐rate regulation utilize the same mechanism, with ppGpp being the common mediator.
Context. In some galaxy clusters, powerful active galactic nuclei (AGN) have blown bubbles with cluster scale extent into the ambient medium. The main pressure support of these bubbles is not known ...to date, but cosmic rays are a viable possibility. For such a scenario copious gamma-ray emission is expected as a tracer of cosmic rays from these systems. Aims. Hydra A, the closest galaxy cluster hosting a cluster scale AGN outburst, located at a redshift of 0.0538, is investigated for being a gamma-ray emitter with the High Energy Stereoscopic System (H.E.S.S.) array and the Fermi Large Area Telescope (Fermi-LAT). Methods. Data obtained in 20.2 h of dedicated H.E.S.S. observations and 38 months of Fermi-LAT data, gathered by its usual all-sky scanning mode, have been analyzed to search for a gamma-ray signal. Results. No signal has been found in either data set. Upper limits on the gamma-ray flux are derived and are compared to models. These are the first limits on gamma-ray emission ever presented for galaxy clusters hosting cluster scale AGN outbursts. Conclusions. The non-detection of Hydra A in gamma-rays has important implications on the particle populations and physical conditions inside the bubbles in this system. For the case of bubbles mainly supported by hadronic cosmic rays, the most favorable scenario, which involves full mixing between cosmic rays and embedding medium, can be excluded. However, hadronic cosmic rays still remain a viable pressure support agent to sustain the bubbles against the thermal pressure of the ambient medium. The largest population of highly-energetic electrons, which are relevant for inverse-Compton gamma-ray production is found in the youngest inner lobes of Hydra A. The limit on the inverse-Compton gamma-ray flux excludes a magnetic field below half of the equipartition value of 16 μG in the inner lobes.
Medical imaging devices often use automated processing that creates and displays a self-normalized image. When improperly executed, normalization can misrepresent information or result in an ...inaccurate analysis. In the case of diagnostic imaging, a false positive in the absence of disease, or a negative finding when disease is present, can produce a detrimental experience for the patient and diminish their health prospects and prognosis. In many clinical settings, a medical technical specialist is trained to operate an imaging device without sufficient background information or understanding of the fundamental theory and processes involved in image creation and signal processing. Here, we describe a user-friendly image processing algorithm that mitigates user bias and allows for true signal to be distinguished from background. For proof-of-principle, we used antibody-targeted molecular imaging of colorectal cancer (CRC) in a mouse model, expressing human MUC1 at tumor sites. Lesion detection was performed using targeted magnetic resonance imaging (MRI) of hyperpolarized silicon particles. Resulting images containing high background and artifacts were then subjected to individualized image post-processing and comparative analysis. Post-acquisition image processing allowed for co-registration of the targeted silicon signal with the anatomical proton magnetic resonance (MR) image. This new methodology allows users to calibrate a set of images, acquired with MRI, and reliably locate CRC tumors in the lower gastrointestinal tract of living mice. The method is expected to be generally useful for distinguishing true signal from background for other cancer types, improving the reliability of diagnostic MRI.
Our purpose was to report outcomes in patients with Child-Pugh B or C (CP B/C) hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT).
Patients with HCC suitable for ...SBRT were prospectively enrolled in the study from 2012 to 2018. Outcomes in patients with CP B/C were analyzed. Cox proportional hazard models were used to compare survival outcomes between baseline CP score and post-SBRT CP score.
Twenty-three patients with CP B/C with a total of 29 HCC tumors were treated with SBRT. Eighty-seven percent of patients were CP B8-C10. Median tumor size was 3.1 cm (range, 1-10 cm). Median dose delivered was 40 Gy in a median of 5 fractions. Eighteen of 23 patients (78.3%) had been previously treated with transarterial chemoembolization. Median follow-up was 14.5 months. Rates of 6- and 12-month local control were 100% and 92.3%, respectively. Six- and 12-month survival rates were 73.9% and 56.5%, respectively. Median survival was 14.5 months overall and 9.2, 22.5, 14.5, and 14.4 months for patients with CP B7, B8, B9, and C10, respectively. No patients exhibited symptoms of classic radiation-induced liver disease. However, 10 patients had CP score progression, with 4 patients (17%) having a ≥2-point increase in CP score by 6 months (or time of censor). There were 7 liver-related deaths, and based on independent review by a hepatologist, 1 of these deaths may have been attributable to SBRT-related liver injury. Fifteen of 23 patients were listed for liver transplant (LT) at the time of SBRT and 9 went on to receive LT with a pathologic complete response rate of 63.6%. Median survival, excluding patients who received LT, was 7.3 months.
SBRT is a reasonable treatment option for carefully selected patients with CP B7-C10. In our small cohort, there was no detectable difference between local control or overall survival and baseline CP score.
Patterned growth of vertically aligned ZnO nanowire arrays on the micrometer and nanometer scale on sapphire and GaN epilayers is reported. In order to control the position and distribution density ...of the ZnO nanowires, Au seeding nanodots are defined, as regular arrays, with the assistance of deposition shadow masks. Electron micrographs reveal that the wires are single crystals having wire axes along the hexagonal
c
-axes. The epitaxial growth of ZnO nanowires on sapphire and GaN films on Si substrates was further verified by cross sectional electron microscopy investigations. Compared to the sapphire case, the perfect epitaxial growth on a GaN film on a Si substrate is believed to be more suitable for potential electronic device applications of ZnO nanowire arrays.
The analysis and prediction of non-canonical structural motifs in RNA is of great importance for an understanding of the function and design of RNA structures. A hierarchical method has been employed ...to generate a large variety of sterically possible conformations for a single-base adenine bulge structure in
A-form DNA and RNA. A systematic conformational search was performed on the isolated bulge motif and neighboring nucleotides under the constraint to fit into a continuous helical structure. These substructures were recombined with double-stranded DNA or RNA. Energy minimization resulted in more than 300 distinct bulge conformations. Energetic evaluation using a solvation model based on the finite-difference Poisson-Boltzmann method identified three basic classes of low-energy structures. The three classes correspond to conformations with the bulge base stacked between flanking nucleotides (I), location of the bulge base in the minor groove (II) and conformations with a continuous stacking of the flanking helices and a looped out bulge base (III). For the looped out class, two subtypes (IIIa and IIIb) with different backbone geometries at the bulge site could be distinguished. The conformation of lowest calculated energy was a class I structure with backbone torsion angles close to those in standard
A-form RNA. Conformations very close to the extra-helical looped out bulge structure determined by X-ray crystallography were also among the low-energy structures. In addition, topologies observed in other experimentally determined bulge structures have been found among low-energy conformers. The implicit solvent model was further tested by comparing an uridine and adenine bulge flanked by guanine:cytosine base-pairs, respectively. In agreement with the experimental observation, a looped out form was found as the energetically most favorable form for the uridine bulge and a stacked conformation in case of the adenine bulge. The inclusion of solvation effects especially electrostatic reaction field contributions turned out to be critically important in order to select realistic low-energy bulge structures from a large number of sterically possible conformations. The results indicate that the approach might be useful to model the three-dimensional structure of non-canonical motifs embedded in double-stranded RNA, in particular, to restrict the number of possible conformations to a manageable number of conformers with energies below a certain threshold.
Objective Endovascular aneurysm repair (EVAR) has become the mainstay of treatment for abdominal aortic aneurysms (AAAs) requiring repair. Delayed rupture after EVAR represents a rare but potentially ...fatal complication. The purpose of this study was to review the frequency and characteristics of patients presenting with secondary rupture and to define the relationship between rupture after EVAR and initial compliance with instructions for use (IFU). Methods This is a retrospective study of a prospectively maintained database. Patients presenting with delayed rupture after EVAR were identified from January 2002 to December 2014. Medical records and imaging were reviewed to define anatomic characteristics and compliance with IFU criteria. Demographics, comorbidities, preoperative imaging, and long-term outcomes were analyzed. Patients were divided into two groups according to compliance with IFU criteria. Outcomes included type of repair (open vs secondary endovascular) as well as perioperative morbidity and mortality. Results A total of 3081 patients underwent EVAR for AAA from 2002 to 2014. Of the 3081 patients, 45 experienced delayed rupture after EVAR. The mean time interval between initial repair and rupture was 38 months. All patients with delayed ruptures had a type Ia endoleak. Mean follow-up after secondary repair was 44.1 months, and overall mortality was 6.7% (n = 3). Patients were divided in two groups according to compliance with IFU criteria: within the IFU and outside the IFU. There was no significant difference in comorbidities between the two groups except smoking, which was more frequent in the outside the IFU group (25% vs 21%; P = .03). Patients repaired outside the IFU had a higher incidence of type Ia endoleak before presenting with a rupture (44% vs 6%; P = .001), more frequently required open repair (44% vs 12%; P = .002), and had higher perioperative mortality (10.3% vs 0%; P = .01). On review of preoperative computed tomography scans, the outside the IFU group had larger aneurysm sac diameters (7.2 vs 5.6 cm; P = .04), larger proximal neck diameters (28 vs 24 mm; P = .01), shorter proximal necks (12 vs 21 mm; P = .007), and a higher degree of neck angulation >40 degrees (56 vs 11%; P < .001). Conclusions Delayed rupture after EVAR is a rare but potentially fatal complication. In patients presenting with secondary rupture, EVAR performed outside the IFU was associated with higher perioperative mortality and need for open repair. Careful selection of patients based on AAA anatomy and adherence to the IFU criteria may reduce the incidence of delayed rupture.
Bulges represent one of the most common non-helical elements in RNA, often displaying a strong degree of phylogenetic conservation, both in location and sequence, within larger RNA molecules. Thus, ...knowledge of the conformation and flexibility of RNA bulges is an important prerequisite for understanding the rules governing the formation of tertiary structure within the larger molecules. In the current investigation, the magnitudes of the bends induced in a 148 base-pair duplex RNA molecule by single, centrally located bulges of varying size (n=1 to 6) and base composition (Anand Unseries) have been determined through the use of transient electric birefringence (TEB). The TEB approach is highly sensitive to the changes in the global shape of RNA (or DNA) helices that accompany the introduction of points of bending or flexibility near the center of the helix. In the current instance, bulge angles deduced from TEB measurements ranged from ∼7° to ∼93°, with the angle increasing with increasingnfor both Anand Unseries. For both Anand Unseries in the absence of Mg2+, the angle increment per added nucleotide varied from ∼20° to ∼8° asnincreased from 1 to 6. These angle increments remained unchanged for the Anseries in the presence of Mg2+; however, the angle increments for the Unseries were reduced by a factor of 2 for all values ofn. Thus the current observations have identified structural transitions in one of the simplest non-helical elements in RNA, transitions that are dependent on both sequence and counterion valence. Finally, the measured bend angles are strongly correlated with the degree of reduction in electrophoretic mobility of bulge-containing RNA helices. The observed correlation was used to obtain a semi-empirical relationship between bend angle and mobility in order that additional angles might be assigned, by interpolation, through the use of gel data alone.
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