Does Orthopaedic Resident Pelvis Fluoroscopy Knowledge improve with testing with a Novel Pelvis Model and Educational website?

Purpose: We tested whether residents would improve in fluoroscopy knowledge and ability after using an inexpensive novel pelvis model and educational website.

Methods: Twenty-four orthopaedic residents were recruited from three United States residency programs and randomised into two groups with equal numbers of juniors and seniors. The OrthoAcademy group received educational materials from a website ( www.

A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.

During replication, lagging strand lesions are initially encountered by high-fidelity DNA polymerase (pol) holoenzymes comprised of pol δ and the PCNA sliding clamp. To proceed unhindered, pol δ holoenzymes must bypass lesions without stalling. This entails dNMP incorporation opposite the lesion (insertion) and the 5' template nucleotide (extension).

T7 RNA polymerase catalyzed transcription of the epimerizable DNA lesion, Fapy•dG and 8-oxo-2'-deoxyguanosine.

Fapy•dG (N6-(2-deoxy-α,β-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine) and 8-OxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) are major products of 2'-deoxyguanosine oxidation. Fapy•dG is unusual in that it exists as a dynamic mixture of anomers. Much less is known about the effects of Fapy•dG than 8-OxodGuo on transcriptional bypass.

Cannulated Screws or Hemiarthroplasty for Femoral Neck Fractures: Is There a Mortality Difference?

Objectives: To determine the difference in mortality and reoperation rate between femoral neck fractures (FNFx) treated with cannulated screw (CS) fixation or hemiarthroplasty (HA).

Design: Retrospective study.

Setting: Institutional registry data from a single Level I trauma center.

8-OxodGuo and Fapy•dG Mutagenicity in Increases Significantly when They Are Part of a Tandem Lesion with 5-Formyl-2'-deoxyuridine.

Tandem lesions, which are defined by two or more contiguously damaged nucleotides, are a hallmark of ionizing radiation. Recently, tandem lesions containing 5-formyl-2'-deoxyuridine (5-fdU) flanked by a 5'-8-OxodGuo or Fapy•dG were discovered, and they are more mutagenic in human cells than the isolated lesions. In the current study, we examined replication of these tandem lesions in .

The Effect of Varying Preoperative Hemoglobin Levels on the Risk of Major Complications and Surgical Site Infections After Single Level Lumbar Fusion.

Introduction: Blood transfusions are associated with an increased risk of complications after lumbar fusion, and current anemia hemoglobin thresholds are not surgery specific. We aimed to calculate single-level lumbar fusion-specific preoperative hemoglobin strata that observe the likelihood of 90-day transfusion and evaluate whether these strata are associated with increased risk of 90-day complications and 2-year infections.

Methods: A national database identified patients undergoing primary single-level lumbar fusion with preoperative hemoglobin values (g/dL).

Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2'-deoxyguanosine.

Formamidopyrimidine (Fapy•dG) is a major lesion arising from oxidation of dG that is produced from a common chemical precursor of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). In human cells, replication of single-stranded shuttle vectors containing Fapy•dG is more mutagenic than 8-OxodGuo. Here, we present the first data regarding promoter dependent RNA polymerase II bypass of Fapy•dG.

Quantification of Intracellular DNA-Protein Cross-Links with N7-Methyl-2'-Deoxyguanosine and Their Contribution to Cytotoxicity.

The major product of DNA-methylating agents, N7-methyl-2'-deoxyguanosine (MdG), is a persistent lesion , but it is not believed to have a large direct physiological impact. However, MdG reacts with histone proteins to form reversible DNA-protein cross-links (DPC), a family of DNA lesions that can significantly threaten cell survival. In this paper, we developed a tandem mass spectrometry method for quantifying the amounts of MdG and DPC in nuclear DNA by taking advantage of their chemical lability and the concurrent release of N7-methylguanine.

Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β.

N6-(2-deoxy-α,β-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood.

Using emerging science to inform risk characterizations for wildlife within current regulatory frameworks.

Many jurisdictions have regulatory frameworks that seek to reduce the effects of environmental exposures of anthropogenic chemicals on terrestrial wildlife (i.e., mammals, birds, reptiles, and amphibians).

Molecular Mechanism of RNA Polymerase II Transcriptional Mutagenesis by the Epimerizable DNA Lesion, Fapy·dG.

Oxidative DNA lesions cause significant detrimental effects on a living species. Two major DNA lesions resulting from dG oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo) and formamidopyrimidine (Fapy·dG), are produced from a common chemical intermediate. Fapy·dG is formed in comparable yields under oxygen-deficient conditions.

Biochemical and Structural Characterization of Fapy•dG Replication by Human DNA Polymerase β.

N6-(2-deoxy-α,β-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood.

The Effect of Socioeconomic Deprivation on Radiographic Deformities in Children With Blount Disease.

Background: Blount disease can occur at any time during the growth process, primarily with a bimodal distribution in children younger than 4 years old and adolescents. The disease process most commonly presents in Black adolescents, with disease severity positively correlated with obesity. Given the known associations among race, obesity, and socioeconomic status, we investigated the relationship between the degree of social deprivation and severity of lower extremity deformities among a community-based cohort with Blount disease.

DNA-Histone Cross-Link Formation via Hole Trapping in Nucleosome Core Particles.

Radical cations (holes) produced in DNA by ionizing radiation and other oxidants yield DNA-protein cross-links (DPCs). Detailed studies of DPC formation in chromatin via this process are lacking. We describe here a comprehensive examination of DPC formation within nucleosome core particles (NCPs), which are the monomeric component of chromatin.

Atraumatic Polycompartment Syndrome Secondary to Cardiogenic Shock: A Case Report.

We report the case of a 53-year-old male who developed polycompartment syndrome (PCS) secondary to cardiogenic shock. After suffering a cardiac arrest, a self-perpetuating cycle of intra-abdominal hypertension (IAH) and vital organ damage led to abdominal compartment syndrome (AbCS), which then contributed to the precipitation of extremity compartment syndrome (CS) in bilateral thighs, legs, forearms, and hands. This report is followed by a review of the literature regarding the pathophysiology of this rare sequela of cardiogenic shock.

Synergistic effects on mutagenicity of tandem lesions containing 8-oxo-7,8-dihydro-2'-deoxyguanosine or Fapy•dG flanked by a 3' 5-formyl-2'-deoxyuridine in human cells.

Modified nucleotides often hinder and/or decrease the fidelity of DNA polymerases. Tandem lesions, which are comprised of DNA modifications at two contiguous nucleotide positions, can be even more detrimental to genome stability. Recently, tandem lesions containing 5-formyl-2'-deoxyuridine (5fdU) flanked at the 5'-position by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo) or N-(2-deoxy-α,β-D-erythropentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy•dG) were discovered.

Deoxyguanosine-Linked Bifunctional Inhibitor of SAMHD1 dNTPase Activity and Nucleic Acid Binding.

Sterile alpha motif histidine-aspartate domain protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase that exists in monomeric, dimeric, and tetrameric forms. It is activated by GTP binding to an A1 allosteric site on each monomer subunit, which induces dimerization, a prerequisite for dNTP-induced tetramerization. SAMHD1 is a validated drug target stemming from its inactivation of many anticancer nucleoside drugs leading to drug resistance.

Photochemical and Single Electron Transfer Generation of 2'-Deoxycytidin-4-yl Radical from Oxime Esters.

A 2'-deoxycytidin-4-yl radical (dC·), a strong oxidant that also abstracts hydrogen atoms from carbon-hydrogen bonds, is produced in a variety of DNA damaging processes. We describe here the independent generation of dC· from oxime esters under UV-irradiation or single electron transfer conditions. Support for this σ-type iminyl radical generation is provided by product studies carried out under aerobic and anaerobic conditions, as well as electron spin resonance (ESR) characterization of dC· in a homogeneous glassy solution at low temperature.

Pain Self-Efficacy (PSEQ) score of <22 is associated with daily opioid use, back pain, disability, and PROMIS scores in patients presenting for spine surgery.

Background Context: Pain self-efficacy, or the belief that one can carry out activities despite pain, has been shown to be associated with back and neck pain severity. However, the literature correlating psychosocial factors to opioid use, barriers to proper opioid use, and Patient-Reported Outcome Measurement Information System (PROMIS) scores is sparse.

Purpose: The primary aim of this study was to determine whether pain self-efficacy is associated with daily opioid use in patients presenting for spine surgery.

8-Oxo-2'-deoxyguanosine Replication in Mutational Hot Spot Sequences of the Gene in Human Cells Is Less Mutagenic than That of the Corresponding Formamidopyrimidine.

7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-OxodGuo) is a ubiquitous DNA damage formed by oxidation of 2'-deoxyguanosine. In this study, plasmid DNA containing 8-OxodGuo located in three mutational hot spots of human cancers, codons 248, 249, and 273 of the tumor suppressor gene, was replicated in HEK 293T cells. 8-OxodGuo was only a weak block of replication, and the bypass was largely error-free.

Histone Deacetylase 1 Inhibition by Peptides Containing a DNA Damage-Induced, Nonenzymatic, Histone Covalent Modification.

Treatment of HeLa cells with the DNA damaging agent, bleomycin (BLM), results in the formation of a nonenzymatic 5-methylene-2-pyrrolone histone covalent modification on lysine residues (K). K is much more electrophilic than other -acyllysine covalent modifications and post-translational modifications, including -acetyllysine (K). Using histone peptides containing K, we show that this modification inhibits the class I histone deacetylase, HDAC1, by reacting with a conserved cysteine (C261) located near the active site.

A Five-Year Cost-Utility Analysis Comparing Synthetic Cage Versus Allograft Use in Anterior Cervical Discectomy and Fusion Surgery for Cervical Spondylotic Myelopathy.

Study Design: Retrospective cost-utility analysis.

Objective: To conduct a cost-analysis comparing synthetic cage (SC) versus allograft (Allo) over a five-year time horizon.

Summary Of Background Data: SC and Allo are two commonly used interbody choices for anterior cervical discectomy and fusion (ACDF) surgery.

Covalent Modification of Bromodomain Proteins by Peptides Containing a DNA Damage-Induced, Histone Post-Translational Modification.

An electrophilic 5-methylene-2-pyrrolone modification (K ) is produced at lysine residues of histone proteins in nucleosome core particles upon reaction with a commonly formed DNA lesion (C4-AP). The nonenzymatic K modification is also generated in the histones of HeLa cells treated with the antitumor agent, bleomycin that oxidizes DNA and forms C4-AP. This nonenzymatic covalent histone modification has the same charge as the N-acetyllysine (K ) modification but is more electrophilic.

Local Alteration of Ionic Strength in a Nucleosome Core Particle and Its Effect on 7-Methyl-2'-deoxyguanosine Depurination.

Positively charged N-terminal histone tails play important roles in maintaining the nucleosome (and chromatin) structure and function. Charge alteration, including those imposed by post-translational modifications, impacts chromatin dynamics, protein binding, and the fate of DNA damage. There is evidence that N-terminal histone tails affect the local ionic environment within a nucleosome core particle (NCP), but this phenomenon is not well understood.

Structural Dynamics of a Common Mutagenic Oxidative DNA Lesion in Duplex DNA and during DNA Replication.

6-(2-Deoxy-α,β-d--pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido pyrimidine (Fapy•dG) is a prevalent form of genomic DNA damage. Fapy•dG is formed in greater amounts under anoxic conditions than the well-studied, chemically related 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo). Fapy•dG is more mutagenic in mammalian cells than 8-oxodGuo.