Altered Metabolism of Polycyclic Aromatic Hydrocarbons by UDP-Glycosyltransferase 3A2 Missense Variants.

The UDP-glycosyltransferase (UGT) family of enzymes are important in the metabolism of a variety of exogenous substances including polycyclic aromatic hydrocarbons (PAHs), a potent class of environmental carcinogens. As compared to the majority of UGT enzymes, which utilize UDP-glucuronic acid as a cosubstrate, UGT3A2 utilizes alternative cosubstrates (UDP-glucose and UDP-xylose). UGT3A2 is expressed in aerodigestive tract tissues and was highly active against multiple PAHs with both cosubstrates.

Structural and Functional Characterization of Dynamic Oligomerization in HMG-CoA Reductase.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), in most organisms, catalyzes the four-electron reduction of the thioester ()-HMG-CoA to the primary alcohol ()-mevalonate, utilizing NADPH as the hydride donor. In some organisms, including the opportunistic lung pathogen , it catalyzes the reverse reaction, utilizing NAD as a hydride acceptor in the oxidation of mevalonate. HMGR has been previously shown to exist as an ensemble of multiple non-additive oligomeric states, each with different levels of enzymatic activity, suggesting that the enzyme exhibits characteristics of the morpheein model of allostery.

Intraoperative brain tumor resection with indocyanine green using augmented microscopy.

Treatment outcomes for brain cancer have seen dismal improvements over the last two decades as evident in available statistical data. Efforts to address this challenge include development of near-infrared contrast agents for improvements in diagnostic and therapeutic modalities. This creates a need for imaging technologies that can support the intraoperative use of such agents.

Biomechanical Comparison of Cadaveric and Commercially Available Synthetic Osteoporotic Bone Analogues in a Locked Plate Fracture Model Under Torsional Loading.

Objectives: Biomechanical studies of osteoporotic bone have used synthetic models rather than cadaveric samples because of decreased variability, increased availability, and overall ease of the use of synthetic models. We compared the torsional mechanical properties of cadaveric osteoporotic bone with those of currently available synthetic osteoporotic bone analogues.

Methods: We tested 12 osteoporotic cadaveric humeri and 6 specimens each of 6 types of synthetic analogues.

Columellar Aesthetics in Open Rhinoplasty.

Detailed descriptions of the ideals of columellar aesthetics and nostril shape are conspicuously lacking from the medical literature. Achieving an aesthetic nasal base is critical to an optimal rhinoplasty result. Deviations in the columella and variations in its width and height lead to distortion of nostril shape and frequently compromise function.

Current Concepts in Filler Injection.

When evaluating the face in thirds, the upper face, midface, and lower face, one may assume the lateral the temple, midface, and lateral mandible as the pillars of these subdivisions. Many of our facial aesthetic procedures address these regions, including the lateral brow lift, midface lift, and lateral face lift. As the use of facial fillers has advanced, more emphasis is placed on the correction of the temples, midlateral face, and lateral jaw line.

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images.

Intraoperative applications of near-infrared (NIR) fluorescent contrast agents can be aided by instrumentation capable of merging the view of surgical field with that of NIR fluorescence. We demonstrate augmented microscopy, an intraoperative imaging technique in which bright-field (real) and electronically processed NIR fluorescence (synthetic) images are merged within the optical path of a stereomicroscope. Under luminance of 100,000 lx, representing typical illumination of the surgical field, the augmented microscope detects 189 nM concentration of indocyanine green and produces a composite of the real and synthetic images within the eyepiece of the microscope at 20 fps.

Integration of indocyanine green videoangiography with operative microscope: augmented reality for interactive assessment of vascular structures and blood flow.

Background: Preservation of adequate blood flow and exclusion of flow from lesions are key concepts of vascular neurosurgery. Indocyanine green (ICG) fluorescence videoangiography is now widely used for the intraoperative assessment of vessel patency.

Objective: Here, we present a proof-of-concept investigation of fluorescence angiography with augmented microscopy enhancement: real-time overlay of fluorescence videoangiography within the white light field of view of conventional operative microscopy.

Surface histidine mutations for the metal affinity purification of a β-carbonic anhydrase.

Metal affinity chromatography using polyhistidine tags is a standard laboratory technique for the general purification of proteins from cellular systems, but there have been no attempts to explore whether the surface character of a protein may be engineered to similar affinity. We present the Arg160His mutation of Haemophilus influenzae carbonic anhydrase (HICA), which mimics the endogenous metal affinity of Escherichia coli carbonic anhydrase (ECCA). The purity and activity of the mutant are reported, and the purification is discussed.

Kinetic characterization of an oxidative, cooperative HMG-CoA reductase from Burkholderia cenocepacia.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a key enzyme in endogenous cholesterol biosynthesis in mammals and isoprenoid biosynthesis via the mevalonate pathway in other eukaryotes, archaea and some eubacteria. In most organisms that express this enzyme, it catalyzes the NAD(P)H-dependent reduction of HMG-CoA to mevalonate. We have cloned and characterized the 6x-His-tagged HMGR from the opportunistic lung pathogen Burkholderia cenocepacia.

How much vertical displacement of the symphysis indicates instability after pelvic injury?

Background: Measures of pubic symphyseal widening are used by at least two classification systems as determinants of injury grade. Recent work has challenged the commonly used parameter of 2.5 cm of pubic symphysis as an accurate marker of pelvic injury grade and has suggested a role of rotation in the flexion-extension plane as a determinant of pelvic stability.

Investigation of multiligamentous knee injury patterns with associated injuries presenting at a level I trauma center.

Objectives: To characterize multiligamentous knee injury patterns and describe associated morbidities.

Design: Retrospective.

Setting: Level I trauma center.

Predictors of normal electrodiagnostic testing in the evaluation of suspected carpal tunnel syndrome.

Electrodiagnostic studies (electromyography and nerve conduction velocity; EMG/NCV) are used to confirm the diagnosis of carpal tunnel syndrome (CTS) and to evaluate its severity. We investigated the hypothesis that normal electrodiagnostic median nerve testing is predicted by 1) Physician pre-test confidence in the diagnosis of CTS, and 2) Puzzling patient factors. One hundred and forty consecutive patients who underwent electrodiagnostic testing to evaluate for possible CTS were reviewed retrospectively.

Correlation of DASH and QuickDASH with measures of psychological distress.

Purpose: In an attempt to shorten the questionnaires given to patients in both clinical and research settings, we studied whether the correlation of commonly used psychological measures was comparable for the standard Disabilities of the Arm, Shoulder, and Hand (DASH) and the shorter QuickDASH questionnaires.

Methods: A cohort of 839 patients with carpal tunnel syndrome, trigger finger, de Quervain's disease, trapeziometacarpal arthrosis, lateral epicondylosis, or a distal radius fracture 2 weeks after surgery, who completed the DASH and 1 or more measures of psychological distress, was created from 10 databases from previously implemented studies. Correlations of the DASH and the QuickDASH with several measures of psychological factors (Center for Epidemiologic Studies Depression Scale [CES-D], Pain Catastrophizing Scale [PCS], and Pain Anxiety Symptoms Scale [PASS-40]) were calculated in both univariate and multivariable analyses.

A survey regarding physician recommendations regarding return to work.

Purpose: Returning patients to work may be influenced by subjective factors and physician bias. The purpose of this study was to determine whether factors such as complaints of pain and patient motivation influence physicians' recommendations regarding return to work or activity.

Methods: One hundred twenty-five members of the American Society for Surgery of the Hand completed an online survey describing a 25-year-old patient with surgically treated diaphyseal fractures of the radius and ulna.

Influence of psychological factors on grip strength.

Purpose: Grip strength is widely used to assess upper-extremity function. Although grip strength is a quantitative measure of function, grip strength is a reflection of both physical impairment as well as subjective, psychological factors. We investigated the determinants of grip strength with the hypothesis that psychological factors are associated with diminished grip strength.

Mass tagging approach for mitochondrial thiol proteins.

A mass tagging approach is described for mitochondrial thiol proteins under nondenaturing conditions. This approach utilizes stable isotope-coded, thiol-reactive (4-iodobutyl)triphenylphosphonium (IBTP) reagents, i.e.

African-American grandmothers as health educators in the family.

More than 18,000 adolescents die each year in the United States from bicycle, motorcycle, car, and truck accidents. This study sought to understand the role of African-American grandmothers as prevention-oriented health educators in the family. Full Model Fitted Regression Analyses were conducted on a sample of African-American grandmothers (N = 105) with 10- to 19-year-old grandchildren.

How sequence defines structure: a crystallographic map of DNA structure and conformation.

The fundamental question of how sequence defines conformation is explicitly answered if the structures of all possible sequences of a macromolecule are determined. We present here a crystallographic screen of all permutations of the inverted repeat DNA sequence d(CCnnnN6N7N8GG), where N6, N7, and N8 are any of the four naturally occurring nucleotides. At this point, 63 of the 64 possible permutations have been crystallized from a defined set of solutions.

The vaccinia virus G1L putative metalloproteinase is essential for viral replication in vivo.

The function of the putative metalloproteinase encoded by the vaccinia virus G1L gene is unknown. To address this question, we have generated a vaccinia virus strain in which expression of the G1L gene is dependent on the addition of tetracycline (TET) when infection proceeds in a cell line expressing the tetracycline repressor. The vvtetOG1L virus replicated similarly to wild-type Western Reserve (WR) virus in these cells when TET was present but was arrested at a late stage in viral maturation in the absence of TET.

Definitions and analysis of DNA Holliday junction geometry.

A number of single-crystal structures have now been solved of the four-stranded antiparallel stacked-X form of the Holliday junction. These structures demonstrate how base sequence, substituents, and drug and ion interactions affect the general conformation of this recombination intermediate. The geometry of junctions had previously been described in terms of a specific set of parameters that include: (i) the angle relating the ends of DNA duplexes arms of the junction (interduplex angle); (ii) the relative rotation of the duplexes about the helix axes of the stacked duplex arms (J(roll)); and (iii) the translation of the duplexes along these helix axes (J(slide)).

Mass spectrometric approaches using electrospray ionization charge states and hydrogen-deuterium exchange for determining protein structures and their conformational changes.

Electrospray ionization (ESI) mass spectrometry (MS) is a powerful analytical tool for elucidating structural details of proteins in solution especially when coupled with amide hydrogen/deuterium (H/D) exchange analysis. ESI charge-state distributions and the envelopes of charges they form from proteins can provide an abundance of information on solution conformations that is not readily available through other biophysical techniques such as near ultraviolet circular dichroism (CD) and tryptophan fluorescence. The most compelling reason for the use of ESI-MS over nuclear magnetic resonance (NMR) for measuring H/D after exchange is that larger proteins and lesser amounts of samples can be studied.

Complications following the "T extensile" approach: a modified extensile approach for acetabular fracture surgery-report of forty-three patients.

Objective: Analyze the prevalence and severity of surgical complications encountered with a modified extended iliofemoral approach, the "T extensile" approach, in the treatment of complex acetabular fractures.

Study Design: Prospective.

Methods: During a sixteen-month study period, forty-three patients with complex acetabular fractures were treated via the T extensile approach.

Hydrogen/deuterium exchange and mass spectrometric analysis of a protein containing multiple disulfide bonds: Solution structure of recombinant macrophage colony stimulating factor-beta (rhM-CSFbeta).

Studies with the homodimeric recombinant human macrophage colony-stimulating factor beta (rhM-CSFbeta), show for the first time that a large number (9) of disulfide linkages can be reduced after amide hydrogen/deuterium (H/D) exchange, and the protein digested and analyzed successfully for the isotopic composition by electrospray mass spectrometry. Analysis of amide H/D after exchange-in shows that in solution the conserved four-helix bundle of (rhM-CSFbeta) has fast and moderately fast exchangeable sections of amide hydrogens in the alphaA helix, and mostly slow exchanging sections of amide hydrogens in the alphaB, alphaC, and alphaD helices. Most of the amide hydrogens in the loop between the beta1 and beta4 sheets exhibited fast or moderately fast exchange, whereas in the amino acid 63-67 loop, located at the interface of the two subunits, the exchange was slow.