Computational Model Validation of Contact Mechanics in Total Ankle Arthroplasty.

Revision rates in total ankle arthroplasty (TAA) are nearly double compared with hip or knee arthroplasty procedures. Contact mechanics for metal-polyethylene articulation in TAA is critical due to the reduced size of the implant and higher expected load, compared with a hip or knee joint. This study was focused on developing a validated computational model to predict contact area in a polyethylene tibial bearing articulating with a metallic talar component in a bicondylar TAA design. Contact area was evaluated at five different flexion angles in an experimental test and in a computational model, per ASTM F2665. The overall contact area values predicted in the computational model matched closely (within 8%) with that measured in the comparator; well within the range reported in the literature. The credibility of the model to sufficiently predict the outputs relative to the experimental data was discussed using the guidelines provided by the recently published ASME V&V 40-2018 standard. Various sensitivities associated with both the model and the comparator, were explored. It was concluded that the validated modeling approach presented in this study demonstrated sufficient accuracy to support the use of modeling for evaluation of contact area of TAA designs. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1063-1069, 2020.

Primary cutaneous non-pigmented mycotic cyst contained in an epidermal inclusion cyst: Case report and review of the literature.

Primary cutaneous mycotic cysts are uncommon dermal or subcutaneous fungal lesions. The most commonly implicated organisms are species within a heterogeneous group of pigmented fungi called dematiaceous fungi. Mycotic cysts usually present as solitary lesions and can be caused by traumatic introduction of fungal elements by foreign bodies or present as a cutaneous manifestation of systemic fungal infections, especially in immunocompromised patients. We present a case of a 63-year-old immunocompetent male who developed a non-erythematous solitary nodule after doing yardwork. Histopathologically, a benign-appearing epidermal inclusion cyst was apparent containing a splinter with keratinous granular debris and no indication of inflammatory host reaction. However, abundant non-pigmented hyphae were visualized after a periodic acid-Schiff stain was performed. This case offers an interesting histopathological view of a non-pigmented mycotic cyst contained within an epidermal inclusion cyst with a true epithelial lining. It also raises the question of whether mycotic cysts caused by non-pigmented fungi are rare or simply under-diagnosed because of their deceptively benign initial appearance. Even in the absence of an inflammatory or granulomatous host response, we recommend investigating for fungal elements in lesions where a splinter or other foreign body material is present in order to avoid misdiagnosis.

The Dosimetric Demise of 97MNB.

Radionuclide differences between ICRP Publication 38 and its succeeding work, ICPR Publication 107, are reviewed. The specific example of the isomer Nb is discussed, examining how dose reporting for this nuclide can be an issue.

Location Modification Factors for Potential Dose Estimation.

A U.S. Department of Energy facility must comply with the National Emission Standard for Hazardous Air Pollutants for radioactive air emissions. The standard is an effective dose of less than 0.1 mSv y to the maximum public receptor. Additionally, a lower dose level may be assigned to a specific emission point in a State issued permit. A method to efficiently estimate the expected dose for future emissions is described. This method is most appropriately applied to a research facility with several emission points with generally low emission levels of numerous isotopes.

Development of criteria used to establish a background environmental monitoring station.

It is generally considered necessary to measure concentrations of contaminants-of-concern at a background location when conducting atmospheric environmental surveillance. This is because it is recognized that measurements of background concentrations can enhance interpretation of environmental monitoring data. Despite the recognized need for background measurements, there is little published guidance available that describes how to identify an appropriate atmospheric background monitoring location. This paper develops generic criteria that can guide the decision making process for identifying suitable locations for background atmospheric monitoring station. Detailed methods for evaluating some of these criteria are also provided and a case study for establishment of an atmospheric background surveillance station as part of an environmental surveillance program is described. While the case study focuses on monitoring for radionuclides, the approach is equally valid for any airborne constituent being monitored. The case study shows that implementation of the developed criteria can result in a good, defensible choice for a background atmospheric monitoring location.

A comparison of dose results from the Clean Air Act Assessment Package-1988, personal computer (CAP88-PC), version 3 to previous versions.

Computer software packages approved by the U.S. Environmental Protection Agency (U.S. EPA), including CAP88-PC, are used by U.S. Department of Energy (U.S. DOE) sites to demonstrate compliance with the radionuclide air emission standard under the Clean Air Act. CAP88-PC version 3, was approved by the U.S. EPA in February 2006 for use by U.S. DOE facilities. Version 3 incorporates several major changes that have the potential to affect calculated doses relative to calculations using earlier versions. This analysis examined the types and magnitudes of changes to dose estimates for specific radionuclides calculated using the version 3 software compared with the previous versions. For parent radionuclides and for the total dose from radionuclide chains, total effective dose calculated with version 3 was compared to effective dose equivalent calculated with previous versions. Various comparisons were also performed to determine which of the updates in version 3 accounted for changes in overall dose estimates. CAP88-PC version 3 would produce substantially different results relative to previous versions of the code for a number of radionuclides, including some isotopes that may be present at U.S. DOE facilities, as well as those used for industrial and medical applications. In general, doses for many radionuclides were lower using version 3 but doses for a few key radionuclides increased relative to the previous versions.

Use of CAP88 at Department of Energy sites.

The U.S. Department of Energy is committed to protecting the public and environment against undue risk from radiation associated with radiological activities conducted under its control. Some U.S. Department of Energy Site activities result in emissions of radioactive materials to the air. CAP88 codes are used to model these emissions and the subsequent maximum estimated dose to a member of the public in the vicinity of the U.S. Department of Energy Site. This paper reviews the use of the CAP88 code at the variety of U.S. Department of Energy sites that use it for compliance reporting under Title 40 of the Code of Federal Regulations Part 61, Subpart H.

Physicians underestimate calcium intake in women.

BACKGROUND AND OBJECTIVES: Personalized nutritional counseling about calcium intake during office encounters requires rapid estimation of calcium intake. We compared the accuracy of physician estimates to a validated calcium intake measure and characterized women whose intakes were incorrectly deemed inadequate by physicians. METHODS: As part of a controlled trial of brief, office-based calcium intake counseling of women, family physicians estimated calcium intake from patients' self-reported intake of dairy food/beverage intake and from their supplement use. We compared estimates to the Short Calcium Questionnaire (SCQ), a validated 7-day dietary recall measure completed by patients. Sensitivity/specificity of physician-estimated calcium intake was estimated by comparison with the SCQ. RESULTS: For 97 women, SCQ rated 32 (33%) as inadequate, 55 (57%) as adequate, and 10 (10%) as excessive. When compared to SCQ, the sensitivity of physician-estimated calcium intake inadequacy was 97% (95% confidence interval [CI]: 94%-100%), specificity was 51% (95% CI: 41%-61%), and positive predictive value was 49% (95% CI: 39%-59%). Women with underestimated intakes were more likely to report a family history of osteoporosis and take a daily multivitamin. The major source of physician underestimation of calcium intake was underestimate of dairy product contribution. CONCLUSIONS: More accurate estimates of dairy-based calcium intake will lead to greater specificity in identifying inadequate calcium intake.

The Livermore phantom history and supplementation.

In vivo monitoring facilities determine the absence or presence of internally entrained radionuclides. To be of greatest utility, the detection systems must detect and quantify the nuclides of interest at levels of interest. Phantoms have been developed to improve measurements at in vivo monitoring facilities. Since the 1970's, the torso phantom originally developed at Lawrence Livermore National Laboratory (LLNL, or simply "Livermore") continues to be a well-used tool at lung monitoring facilities, especially for the detection of low-energy photons from transuranics. The history of its development from need through design development and current availability is summarized. The authors have taken the LLNL phantom one step further by scanning the phantom surface and announce the availability of the scan files on the Internet.

Barriers to supplemental calcium use among women in suburban family practice: a report from the Cleveland Clinic Ambulatory Research Network (CleAR-eN).

BACKGROUND: The majority of adult women in the United States fail to meet daily calcium intake recommendations. This study was undertaken to (1) identify predictors of calcium supplement use versus non-use, (2) understand barriers to calcium supplementation, and (3) determine the potential impact of physician recommendation on calcium supplement use. METHODS: Surveys were self-administered by 185 women, ages 20 to 64, presenting consecutively for care at 6 suburban community-based family medicine practices within the Cleveland Clinic Ambulatory Research Network (CleAR-eN). We compared demographic characteristics, health beliefs, and health behaviors of those women who reported never using calcium supplements with those who presently took calcium supplements. Women who never took calcium were also queried about reasons for non-use and whether physician recommendation would influence their adoption of calcium supplementation. RESULTS: Multivitamin use, self-perceived risk of osteoporosis, and age were independent predictors of calcium supplement use. Leading barriers for never-users were lack of knowledge about the need/importance of increasing calcium intake, lack of motivation to start supplements, and the belief that their dietary calcium intake alone was sufficient. Ninety-six percent of never-users reported that they would consider taking a calcium supplement if recommended by their physician. CONCLUSIONS: Many patient-identified barriers to calcium supplementation seem amenable to focused and brief office-based interventions that could increase the number of women meeting calcium intake guidelines.

Regulation of ghrelin structure and membrane binding by phosphorylation.

The peptide hormone ghrelin requires Ser-3 acylation for receptor binding, orexigenic and anti-inflammatory effects. Functions of desacylghrelin are less well understood. In vitro kinase assays reveal that the evolutionarily conserved Ser-18 in the basic C-terminus is an excellent substrate for protein kinase C. Circular dichroism reveals that desacylghrelin is approximately 12% helical in aqueous solution and approximately 50% helical in trifluoroethanol. Ser-18-phosphorylation, Ser-18-Ala substitution, or Ser-3-acylation reduces the helical character in trifluoroethanol to approximately 24%. Both ghrelin and desacylghrelin bind to phosphatidylcholine:phosphatidylserine sucrose-loaded vesicles in a phosphatidylserine-dependent manner. Phosphoghrelin and phosphodesacylghrelin show greatly diminished phosphatidylserine-dependent binding. These results are consistent with binding of ghrelin and desacylghrelin to acidic lipids via the basic face of an amphipathic helix with Ser-18 phosphorylation disrupting both helical character and membrane binding.

Interactions of annexins with the mu subunits of the clathrin assembly proteins.

A number of biochemical and genetic studies have suggested that certain annexins play important roles in the endocytic pathway, possibly involving the generation, localization, or fusion of endocytic compartments. In a yeast two-hybrid screen for proteins that interact with the N-terminal domain of annexin A2 we identified the mu2 subunit of the clathrin assembly protein complex AP-2. The interaction depended upon two copies of a Yxx phi amino acid sequence motif (Y = tyrosine, x = variable residue, phi = bulky, hydrophobic residue) in the annexin that is also characteristic of the binding site for mu2 on the cytoplasmic domains of transmembrane receptors. The interaction between mu2 and full-length annexin A2 was demonstrated in vitro to be direct, to require calcium, and to be functional in the sense that annexin A2 was able to recruit the mu2 to immobilized lipids. Examination of other annexins and mu subunits demonstrated that annexin A2 also binds the mu1 subunit of the AP-1 complex, that annexin A6 binds mu1 and mu2, and that annexin A1 binds only mu1. We propose that annexins can "masquerade" as transmembrane receptors when they are attached to membranes in the presence of calcium and that they might therefore function to initiate calcium-regulated coated pit formation at the cell surface or on intracellular organelles.

Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif.

We provide evidence that copines, members of a ubiquitous family of calcium-dependent, membrane-binding proteins, may represent a universal transduction pathway for calcium signaling because we find copines are capable of interacting with a wide variety of "target" proteins including MEK1, protein phosphatase 5, and the CDC42-regulated kinase, that are themselves components of intracellular signaling pathways. The copine target proteins were identified by yeast two-hybrid screening and the interactions were verified in vitro using purified proteins. In the majority of cases the copine binds to a domain of the target protein that is predicted to form a characteristic coiled-coil. A consensus sequence for the coiled-coil copine-binding site was derived and found to have predictive value for identifying new copine targets. We also show that interaction with copines may result in recruitment of target proteins to membrane surfaces and regulation of the enzymatic activities of target proteins.