Image quality of photon-counting detector CT virtual monoenergetic and polyenergetic reconstructions for head and neck CT angiography.

We compared image quality of head and neck CT angiography (CTA) obtained with a photon-counting detector CT (PCD-CT), including virtual monoenergetic images and polyenergetic reconstructions, and conventional energy-integrating detectors CT (EID-CT) in three patients. PCD-CT monoenergetic reconstructions at 70 keV and lower provided excellent image quality, with improved signal-to-noise and contrast-to-noise compared to EID-CT and PCD-CT polyenergetic reconstructions. PCD-CT may enable radiation dose and iodinated contrast dose reduction for cerebrovascular imaging.

A Randomized Controlled Trial Examining the Effect of Topical Refrigerant Spray on the Perception of an Instantaneous Noxious Stimulus.

Purpose: Topical refrigerant spray is commonly used with routine hand injections despite mixed evidence about its efficacy in reducing the pain experience. We hypothesize that the use of topical refrigerant spray decreases the pain experience of an instantaneous noxious stimulus. Methods: Eighty adult volunteer participants were enrolled in the study. We constructed an instrument using the smooth end of a Kirschner wire mounted to the spring of a ballpoint pen to apply an instantaneous noxious stimulus to the long (middle) finger proximal nail fold. Participants completed two trials and were randomized to receive the topical refrigerant spray before either the first or second stimulus and on either the left or right side. Participants were asked to rate the pain of each experience using an 11-point Likert scale and indicate which condition they preferred, if any. Results: The mean pain ratings for the spray and no-spray conditions were 2.0 and 4.3, respectively, giving a mean difference of -2.3 (P < .001, α = 0.05). Subgroup analysis showed no significant effect of sex or medical versus nonmedical occupation (P = .28 and .11 respectively) on the mean difference in pain rating between the two conditions. Participants who received the spray first had a higher mean difference in pain rating (2.7) than that in those who received it second (1.9). Fifty-nine participants preferred the spray, whereas 21 participants either preferred no spray or had no preference (P < .0001). Conclusions: The use of topical refrigerant spray significantly decreased the perception of pain from an instantaneous noxious stimulus. A significant majority of participants also preferred the topical refrigerant spray condition. The use of topical refrigerant spray for painful procedures, such as needle insertions, may improve the overall patient experience. Type of study/level of evidence: Therapeutic I.

PET and FRET utility of an amino acid pair: tryptophan and 4-cyanotryptophan.

Methods based on fluorescence resonance energy transfer (FRET) and photo-induced electron transfer (PET) are widely used in the biological sciences, employing mostly dye-based FRET and PET pairs. While very useful and important, dye-based reporters are not always applicable without concern, for example, in cases where the fluorophore size needs to be minimized. Therefore, development and characterization of smaller, ideally amino acid-based PET and FRET pairs will expand the biological spectroscopy toolbox to enable new applications. Herein, we show that, depending on the excitation wavelength, tryptophan and 4-cyanotrptophan can interact with each other via the mechanism of either energy or electron transfer, hence constituting a dual FRET and PET pair. The biological utility of this amino acid pair is further demonstrated by applying it to study the end-to-end collision rate of a short peptide, the mode of interaction between a ligand and BSA, and the activity of a protease.

4-Cyanoindole-2'-deoxyribonucleoside as a Dual Fluorescence and Infrared Probe of DNA Structure and Dynamics.

Unnatural nucleosides possessing unique spectroscopic properties that mimic natural nucleobases in both size and chemical structure are ideally suited for spectroscopic measurements of DNA/RNA structure and dynamics in a site-specific manner. However, such unnatural nucleosides are scarce, which prompts us to explore the utility of a recently found unnatural nucleoside, 4-cyanoindole-2'-deoxyribonucleoside (4CNI-NS), as a site-specific spectroscopic probe of DNA. A recent study revealed that 4CNI-NS is a universal nucleobase that maintains the high fluorescence quantum yield of 4-cyanoindole and that among the four natural nucleobases, only guanine can significantly quench its fluorescence. Herein, we further show that the C≡N stretching frequency of 4CNI-NS is sensitive to the local environment, making it a useful site-specific infrared probe of oligonucleotides. In addition, we demonstrate that the fluorescence-quencher pair formed by 4CNI-NS and guanine can be used to quantitatively assess the binding affinity of a single-stranded DNA to the protein system of interest via fluorescence spectroscopy, among other applications. We believe that this fluorescence binding assay is especially useful as its potentiality allows high-throughput screening of DNA⁻protein interactions.

Newfound effect of N-acetylaspartate in preventing and reversing aggregation of amyloid-beta in vitro.

Although N-acetylaspartate (NAA) has long been recognized as the most abundant amino acid in neurons by far, its primary role has remained a mystery. Based on its unique tertiary structure, we explored the potential of NAA to modulate aggregation of amyloid-beta (Aß) peptide 1-42 via multiple corroborating aggregation assays along with electron microscopy. Thioflavin-T fluorescence assay demonstrated that at physiological concentrations, NAA substantially inhibited the initiation of Aß fibril formation. In addition, NAA added after 25 min of Aß aggregation was shown to break up preformed fibrils. Electron microscopy analysis confirmed the absence of mature fibrils following NAA treatment. Furthermore, fluorescence correlation spectroscopy and dynamic light scattering measurements confirmed significant reductions in Aß fibril hydrodynamic radius following treatment with NAA. These results suggest that physiological levels of NAA could play an important role in controlling Aß aggregation in vivo where they are both found in the same neuronal compartments.

A 31-residue peptide induces aggregation of tau's microtubule-binding region in cells.

The self-propagation of misfolded conformations of tau underlies neurodegenerative diseases, including Alzheimer's. There is considerable interest in discovering the minimal sequence and active conformational nucleus that defines this self-propagating event. The microtubule-binding region, spanning residues 244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Further dissection of the amyloid-forming region to a hexapeptide from the third microtubule-binding repeat resulted in a peptide that rapidly forms fibrils in vitro. We show that this peptide lacks the ability to seed aggregation of tau244-372 in cells. However, as the hexapeptide is gradually extended to 31 residues, the peptides aggregate more slowly and gain potent activity to induce aggregation of tau244-372 in cells. X-ray fibre diffraction, hydrogen-deuterium exchange and solid-state NMR studies map the beta-forming region to a 25-residue sequence. Thus, the nucleus for self-propagating aggregation of tau244-372 in cells is packaged in a remarkably small peptide.

Fermi resonance as a means to determine the hydrogen-bonding status of two infrared probes.

The C[double bond, length as m-dash]O/C[triple bond, length as m-dash]N stretching vibration arising from a carbonyl/nitrile functional group in various molecular systems has been frequently used to assess, for example, local hydrogen-bonding interactions, among other applications. However, in practice it is not always easy to ascertain whether the carbonyl or nitrile group in question is engaged in such interactions. Herein, we use 4-cyanoindole and cyclopentanone as models to show that, when a fundamental C[double bond, length as m-dash]O or C[triple bond, length as m-dash]N stretching mode is involved in Fermi resonance, the underlying vibrational coupling constant (W) is a convenient reporter of the hydrogen-bonding status of the corresponding carbonyl or nitrile group. Specifically, we find that for both groups a W value of 7.7 cm-1 or greater is indicative of their involvement in hydrogen-bonding interactions. Furthermore, we find that, as observed in similar studies, the Fermi resonance coupling leads to quantum beats in the two-dimensional infrared spectra of 4-cyanoindole in isopropanol, with a period of about 1.9 ps.

Kinetic Isotope Effect Provides Insight into the Vibrational Relaxation Mechanism of Aromatic Molecules: Application to Cyano-phenylalanine.

Varying the reduced mass of an oscillator via isotopic substitution provides a convenient means to alter its vibrational frequency and hence has found wide applications. Herein, we show that this method can also help delineate the vibrational relaxation mechanism, using four isotopomers of the unnatural amino acid p-cyano-phenylalanine (Phe-CN) as models. In water, the nitrile stretching frequencies of these isotopomers, Phe-(12)C(14)N (1), Phe-(12)C(15)N (2), Phe-(13)C(14)N (3), and Phe-(13)C(15)N (4), are found to be equally separated by ∼27 cm(-1), whereas their vibrational lifetimes are determined to be 4.0 ± 0.2 (1), 2.2 ± 0.1 (2), 3.4 ± 0.2 (3), and 7.9 ± 0.5 ps (4), respectively. We find that an empirical relationship that considers the effective reduced mass of CN can accurately account for the observed frequency gaps, while the vibrational lifetime distribution, which suggests an intramolecular relaxation mechanism, can be rationalized by the order-specific density of states near the CN stretching frequency.

Opioid consumption following outpatient upper extremity surgery.

PURPOSE: After elective outpatient upper extremity surgery, patients' need for opioid analgesic medication may be considerably less than typically dispensed. Our goal for this study was to evaluate pain control and quantify the amount of leftover pain medication. METHODS: We recruited patients scheduled for elective outpatient upper extremity surgery, who met the inclusion criteria, to participate in a phone interview 7 to 14 days after surgery. Information collected included age, gender, procedure performed, analgesic medication and regimen prescribed, satisfaction with pain control, number of tablets remaining, reasons for not taking medication, other analgesic medications used, payer classification, and any adverse drug reactions. RESULTS: A total of 287 eligible subjects consented to participate. Of these, 36 patients failed phone contact and 1 patient canceled surgery, which left 250 patients who completed the study. Oxycodone, hydrocodone, and propoxyphene accounted for over 95% of the prescription medications, with adequate pain control reported by 230 (92%) patients. Patients most frequently received 30 pills. Patients undergoing bone procedures reported the highest medication use (14 pills), whereas patients undergoing soft tissue procedures reported the lowest use (9 pills). Over half of the subjects reported taking the opioid medication for 2 days or less. Medicare patients consumed significantly less medication (7 pills, P < .05) than patients covered by all other types of insurance. Overall, patients consumed a mean of 10 opioid pills, whereas 19 pills per subject were reported unused, which resulted in 4,639 leftover tablets for the entire cohort. CONCLUSIONS: Our data show that excess opioid analgesics are made available after elective upper extremity surgery and could potentially become a source for diversion. A prescription of 30 opioid pills for outpatient surgery appears excessive and unnecessary, especially for soft tissue procedures of the hand and wrist. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.

Matrix and polymer soft-landing isolation of selected acids with pyridine and poly(4-vinylpyridine): a comparative infrared spectroscopic study of hydrogen bonding.

Hydrogen bonding plays a key role in the formation of nanostructures, as it is the "glue" between layers that are built by the layer-by-layer technique. Poly(4-vinylpyridine) (PVP) is one of the most commonly used polymers in these sandwich-structured films, often in conjunction with poly(carboxylic acid)s such as poly(acrylic acid) in the PVP/PAA interpolymer complex. In addition, PVP is commonly used as a polymer matrix for embedding semiconductor nanoparticles. In this study, hydrogen-bonded complexes of water, formic acid, and pentachlorocyclopropane, with pyridine in a traditional matrix isolation experiment and PVP in a novel "polymer soft-landing" isolation experiment, have been characterized for the first time at 16 K. Changes in vibrational modes of the proton donor species and in some cases pyridine modes provided ample evidence for complex formation. In the case of water and pentachlorocyclopropane, the matrix and polymer soft-landing results were quite similar, whereas formic acid formed a significantly different complex with pyridine in the argon matrix than with the pyridine ring on the PVP polymer. This work demonstrates clearly the benefit of using both the conventional matrix isolation technique and our polymer soft-landing variation in tandem to probe the structure of these complexes and thus elucidate the nature of the C-H···N, C-H···O═C, and O-H···N linkages.

Scaphoid excision and limited wrist fusion: a comparison of K-wire and circular plate fixation.

The purpose of this study was to compare the clinical outcome, union rate, and complications of a consecutive series of Scaphoid excision and limited wrist arthrodesis performed by a single surgeon using distal radius bone graft and K-wires or circular plate fixation. A sequential series of ten patients(11 wrists) who were stabilized with temporary K-wires were compared to 11 patients (11 wrists) who were stabilized with a circular plate. Minimum follow-up was 1 year. One patient in the K-wire group was converted to a wrist fusion. Six of the remaining ten patients in the K-wire fixation group and 8 of the 11 patients in the circular plate fixation group returned for the following blinded evaluations: Quick DASH, analog pain scale, range of motion, grip and pinch strength, plain x-ray, and multi-detector computed tomography evaluation. One non-union occurred in the K-wire group. There were no non-unions in the circular plate fixation group. There was no difference in any of remaining measures or rate of complications. This study shows that equivalent results can be obtained using circular plate fixation compared to K-wires when equivalent bone graft source and fusion technique are used. If K-wire removal requires a return to the OR, circular plate fixation is more cost-effective.

Resistance to activated protein C and digital thrombosis.

Resistance to activated protein C is a newly described genetic coagulation disorder previously only reported in patients with venous thromboembolism or central arterial embolism (cerebral or coronary). We report this defect in association with digital artery thrombosis and describe the pathophysiology of this disorder.