Background Large volumes of dilute local anesthesia are increasingly used not only for liposuction but also for other large cutaneous surgeries, including skin cancer excision. Although the lidocaine ...serum levels and peaks after injection of tumescent anesthesia in the trunk were shown to be safe even when used in high doses, the levels after use of less dilute (1% lidocaine) solutions for facial cancer surgery have not been described. Objective We sought to ascertain whether perioperative peak lidocaine levels during Mohs micrographic surgery approach thresholds for lidocaine toxicity. Methods In this prospective cohort study, each Mohs micrographic procedure was commenced per routine protocol, with use of injectable 1% lidocaine with 1:200,000 epinephrine and 1:10 8.4% bicarbonate for local anesthesia. Six peripheral blood draws of 5 mL each were performed and sent for serum lidocaine concentration measurement. Blood draws were obtained before and after the first two stages of Mohs micrographic surgery, and before and after the third stage or wound repair, as appropriate. Subjects and investigators reported any symptoms or signs of lidocaine toxicity. The main outcome measures include: (1) number of subjects exhibiting at least one level higher than the threshold for toxicity; and (2) sustained elevated lidocaine levels in one or more subjects. Results Mean total lidocaine volume per subject was 15 mL (range: 5-48 mL). The highest peak serum lidocaine level detected at any time point (blood draw) for any subject was 0.3 μg/mL. Mean serum lidocaine level for all 6 time points was less than 0.1 μg/mL and was thus not detected. Detectable lidocaine levels were found to be associated with higher mean ( P = .028) and median ( P = .008) total lidocaine doses. Because no toxic levels were detected, it was not possible to measure sustained high lidocaine levels. Limitations Limitations of this study include the lack of use of very concentrated (eg, 2% vs 1%) lidocaine solution. Conclusions Lidocaine use during Mohs micrographic surgery does not appear to result in serum lidocaine levels approaching toxic levels even when relatively high total lidocaine doses are used. There is an association between higher total lidocaine dose and perioperative peak serum lidocaine level.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
2.
Defining skin cancer local recurrence Wysong, Ashley; Higgins, Shauna; Blalock, Travis W. ...
Journal of the American Academy of Dermatology,
August 2019, 2019-Aug, 2019-08-00, 20190801, Volume:
81, Issue:
2
Journal Article
Peer reviewed
Definitions of skin cancer recurrence are variable and nonstandardized, which can lead to inconsistent and potentially inappropriate management of tumors of uncertain recurrence status. Defining ...recurrence is important given the potential association with metastasis in both melanoma and nonmelanoma skin cancer. A review of the literature across multiple disciplines involved in the care of skin cancer patients reveals that although criteria for recurrence are provided in the majority of cases, most are vague and inconsistent. Given the presumably increased morbidity and mortality associated with recurrent tumors, accurate identification and appropriate management is paramount. In addition, value-based health care necessitates validated and relevant outcome measures that are standardized and, thus, enable tracking of comparable and corresponding outcomes. A universal definition of localized skin cancer recurrence would ultimately allow for improved surveillance and informed therapeutic strategies to decrease morbidity and mortality of patients afflicted with skin cancer, the most common cancer nationwide.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Quantum size effects can provide information related to the film-substrate interface occurring in thin film systems. Pb films have been grown upon the Ag-root 3/Si(111) reconstruction by molecular ...beam epitaxy and studied with angle-resolved photoemission over a range of coverages up to 20 monolayers. The confinement of electrons within the Pb overlayers produces sharp quantum well states which exhibit atomic-layer resolution. Layer counting permits an absolute determination of the film thicknesses. The binding energies of these quantum well states differ significantly from those observed in recent studies of the Pb/Si(111) system, as the presence of Ag at the interface alters the film-substrate interface boundary conditions.
Full text
Available for:
CMK, CTK, FMFMET, NUK, UL, UM, UPUK
As the thickness of a metallic film decreases to the atomic scale, the confinement of the film's electrons by its boundaries gives rise to discrete electronic states, known as quantum well states, ...which dominate the film properties. This work investigates the use of film-substrate boundary modification as a means to control the film properties through the manipulation of its quantum well states. Specifically, the Schottky barrier heights and thermal stability temperatures for Pb(111) films grown on metal-reconstructed Si(111) substrates are shown to be determined by the interfacial conditions produced by the various Si-terminating metals (Au, Ag, In, and Pb), known as interfactants. These properties are probed experimentally with angle-resolved photoemission spectroscopy using vacuum ultraviolet synchrotron radiation. An analysis of the measured quantum well energy levels and peak widths determines the height of the Schottky barrier, the rectifying energy barrier at a metal-semiconductor junction. A calculation based on the known interface chemistry and the electronegativity yields predicted barrier heights in good agreement with the experiment. These results demonstrate that the Schottky barrier height can be tuned to a desired value through an appropriate selection of interfactant. Extending the exploration of interfactant effects to physical properties, the thermal stability temperatures of Pb films are measured with photoemission. The quantized electronic structure in Pb films causes the thermal stability to oscillate with an approximate bilayer period. A comparison among the systems reveals a phase reversal and an amplitude deviation in the stability temperatures. For Pb/In-special characters omitted × special characters omitted/Si(111), films made of odd numbers of atomic layers are observed to be more stable than the even ones, but this trend is reversed for the other cases studied. For Pb/Au-6×6/Si(111), the maximum stability temperatures are in excess of room temperature, unlike the other systems. These results show that the temperature-dependent thermal stability behaviors can be controlled by interfacial engineering.
ABSTRACT We have discovered heavy obscuration in the dual active galactic nucleus (AGN) in the Swift/Burst Alert Telescope (BAT) source SWIFT J2028.5+2543 using Nuclear Spectroscopic Telescope Array ...(NuSTAR). While an early XMM-Newton study suggested the emission was mainly from NGC 6921, the superior spatial resolution of NuSTAR above 10 keV resolves the Swift/BAT emission into two sources associated with the nearby galaxies MCG +04-48-002 and NGC 6921 (z = 0.014) with a projected separation of 25.3 kpc (91″). NuSTAR's sensitivity above 10 keV finds both are heavily obscured to Compton-thick levels (NH (1-2) × 1024 cm−2) and contribute equally to the BAT detection ( L 10 − 50 keV int 6 × 1042 erg s−1). The observed luminosity of both sources is severely diminished in the 2-10 keV band ( L 2 − 10 keV obs < 0.1 × L 2 − 10 keV int ), illustrating the importance of >10 keV surveys like those with NuSTAR and Swift/BAT. Compared to archival X-ray data, MCG +04-48-002 shows significant variability (>3) between observations. Despite being bright X-ray AGNs, they are difficult to detect using optical emission-line diagnostics because MCG +04-48-002 is identified as a starburst/composite because of the high rates of star formation from a luminous infrared galaxy while NGC 6921 is only classified as a LINER using line detection limits. SWIFT J2028.5+2543 is the first dual AGN resolved above 10 keV and is the second most heavily obscured dual AGN discovered to date in the X-rays other than NGC 6240.
The main nuclear factor kappa B transcription factor family members RelA–p50 heterodimer and RelA homodimer have different biological functions and show different transcriptional activation profiles. ...To investigate whether the two family members adopt a similar conformation in their free states, we performed hydrogen–deuterium exchange mass spectrometry, all-atom molecular dynamics simulations, and stopped-flow binding kinetics experiments. Surprisingly, the N-terminal DNA-binding domains adopt an open conformation in RelA–p50 but a closed conformation in RelA homodimer. Both hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations indicate the formation of an interface between the N-terminal DNA-binding domains only in the RelA homodimer. Such an interface would be expected to impede DNA binding, and stopped-flow binding kinetics show that association of DNA is slower for the homodimer as compared to the heterodimer. Our results show that the DNA-binding cavity in the RelA–p50 heterodimer is open for DNA binding, whereas in the RelA homodimer, it is occluded.
Display omitted
•Structures of RelA-containing NFκB dimers have not been examined to date because all crystal structures have the NFκB dimer in complex with either DNA or inhibitor and the free dimers do not crystallize. To investigate the dynamics of free Rel-A-containing NFκB dimers in solution, we performed amide exchange experiments and molecular dynamics simulations.•NFκB dimers appear very dynamic in the absence of DNA. In particular, the DNA-binding domains (DBDs) reorient due to the flexible linker that connects them to the dimerization domain.•Amide exchange (HDXMS) shows much less exchange in the RelA homodimer DBDs than in the RelA–p50 DBDs.•The RelA–p50 heterodimer DBDs move away from each other during the MD simulations, whereas the RelA homodimer DBDs move toward each other. The MD results are consistent with the HDXMS and provide an explanation for the dramatically reduced exchange in the homodimer—the homodimer DBDs actually form an interface that is protected from exchange.•The observation of such different DNA-binding cavities in the two RelA-containing NFκBs suggested that DNA may associate more slowly with the RelA homodimer, and stopped-flow measurements show significantly slower association with the RelA homodimer. Taken together, the results help explain a long-standing puzzle in the NFκB field, why DNA binds more weakly to the RelA homodimer than to the RelA–p50 heterodimer.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We present the analysis of the first Nuclear Spectroscopic Telescope Array observations (∼220 ks), simultaneous with the last Suzaku observations (∼50 ks), of the active galactic nucleus of the ...bright Seyfert 1 galaxy Mrk 509. The time-averaged spectrum in the 1-79 keV X-ray band is dominated by a power-law continuum (Γ ∼ 1.8-1.9), a strong soft excess around 1 keV, and signatures of X-ray reflection in the form of Fe K emission (∼6.4 keV), an Fe K absorption edge (∼7.1 keV), and a Compton hump due to electron scattering (∼20-30 keV). We show that these data can be described by two very different prescriptions for the soft excess: a warm (kT ∼ 0.5-1 keV) and optically thick (τ ∼ 10-20) Comptonizing corona or a relativistically blurred ionized reflection spectrum from the inner regions of the accretion disk. While these two scenarios cannot be distinguished based on their fit statistics, we argue that the parameters required by the warm corona model are physically incompatible with the conditions of standard coronae. Detailed photoionization calculations show that even in the most favorable conditions, the warm corona should produce strong absorption in the observed spectrum. On the other hand, while the relativistic reflection model provides a satisfactory description of the data, it also requires extreme parameters, such as maximum black hole spin, a very low and compact hot corona, and a very high density for the inner accretion disk. Deeper observations of this source are thus necessary to confirm the presence of relativistic reflection and further understand the nature of its soft excess.
PDF
