A Modified Delphi Study for Curricular Content of Simulation-Based Medical Education for Pediatric Residency Programs.

Objective: We sought to establish core knowledge topics and skills that are important to teach pediatric residents using simulation-based medical education (SBME).

Methods: We conducted a modified Delphi process with experts in pediatric SBME. Content items were adapted from the American Board of Pediatrics certifying exam content and curricular components from pediatric entrustable professional activities (EPAs).

Investigating the Heaviest Halogen: Lessons Learned from Modeling the Electronic Structure of Astatine's Small Molecules.

We present a systematic study of electron-correlation and relativistic effects in diatomic molecular species of the heaviest halogen astatine (At) within relativistic single- and multireference coupled-cluster approaches and relativistic density functional theory. We establish revised reference ab initio data for the ground states of At, HAt, AtAu, and AtO using a highly accurate relativistic effective core potential model and in-house basis sets developed for accurate modeling of molecules with large spin-orbit effects. Spin-dependent relativistic effects on chemical bonding in the ground state are comparable to the binding energy or even exceed it in At.

Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen.

Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18-Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus.

Epidemiology of Bleeding in Critically Ill Children.

Objective: To determine the epidemiology of bleeding in critically ill children.

Study Design: We conducted a cohort study of children <18 years old admitted to the pediatric intensive care unit for >24 hours and without clinically relevant bleed (CRB) on admission. CRB was defined as resulting in severe physiologic derangements, occurring at a critical site or requiring major therapeutic interventions.

DNA G-quadruplexes show strong interaction with DNA methyltransferases in vitro.

The DNA methyltransferase enzymes (DNMTs) catalyzing cytosine methylation do so at specific locations of the genome, although with some level of redundancy. The de novo methyltransferases DNMT3A and 3B play a vital role in methylating the genome of the developing embryo in regions devoid of methylation marks. The ability of DNMTs to colocalize at sites of DNA damage is suggestive that recognition of mispaired bases and unusual structures is inherent to the function of these proteins.

Corticosteroid-binding globulin (CBG) reactive centre loop antibodies and surface plasmon resonance interrogate the proposed heat dependent "flip-flop" mechanism of human CBG.

Corticosteroid-binding globulin (CBG) is the predominant carrier of cortisol in circulation and is a non-inhibitory member of the serpin superfamily of serine protease inhibitors. In the stressed or "S" conformation, CBG possesses an intact exposed reactive centre loop (RCL) that can be irreversibly cleaved by elastase released from activated human neutrophils whereupon it adopts a relaxed or "R" conformation. The latter conformation has decreased affinity for cortisol, allowing the release of the majority of cortisol at sites of inflammation.

Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005.

Purpose: Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma.

A surface plasmon resonance assay for measurement of neuraminidase inhibition, sensitivity of wild-type influenza neuraminidase and its H274Y mutant to the antiviral drugs zanamivir and oseltamivir.

Antiviral resistance is currently monitored by a labelled enzymatic assay, which can give inconsistent results because of the short half-life of the labelled product, and variations in assay conditions. In this paper, we describe a competitive surface plasmon resonance (SPR) inhibition assay for measuring the sensitivities of wild-type neuraminidase (WT NA) and the H274Y (histidine 274 tyrosine) NA mutant to antiviral drugs. The two NA isoforms were expressed in High-five™ (Trichoplusia ni) insect cells.

Development of a surface plasmon resonance assay to measure the binding affinity of wild-type influenza neuraminidase and its H274Y mutant to the antiviral drug zanamivir.

Influenza is one of the most common infections of the upper respiratory tract. Antiviral drugs that are currently used to treat influenza, such as oseltamivir and zanamivir, are neuraminidase (NA) inhibitors. However, the virus may develop resistance through single-point mutations of NA.

Insulin receptor-insulin interaction kinetics using multiplex surface plasmon resonance.

Type 2 diabetes affects millions of people worldwide, and measuring the kinetics of insulin receptor-insulin interactions is critical to improving our understanding of this disease. In this paper, we describe, for the first time, a rapid, real-time, multiplex surface plasmon resonance (SPR) assay for studying the interaction between insulin and the insulin receptor ectodomain, isoform A (eIR-A). We used a scaffold approach in which anti-insulin receptor monoclonal antibody 83-7 (Abcam, Cambridge, UK) was first immobilized on the SPR sensorchip by amine coupling, followed by eIR-A capture.

A Gel Filtration-Based Method for the Purification of Infectious Rotavirus Particles for Environmental Research Applications.

This article describes a rapid method for purifying infectious rotavirus particles from cell culture for environmental research. The method is based on size-exclusion chromatography using TOSOH TSKgel G5000PWXL-CP with a TSKgel Size Exclusion G2500PWxl guard column, set up on an AKTA Explorer10. Four peaks were identified from the chromatogram and the corresponding fractions were collected and analysed by electron microscopy, 1-step quantitative reverse transcription polymerase chain reaction (RT-PCR) and qNano measurement.

Lenalidomide stops progression of multifocal epithelioid hemangioendothelioma including intracranial disease.

Epithelioid Hemangioendothelioma (EH) is a rare soft-tissue tumor which may present as an isolated tumor or can spread to affect internal organs. The course of EH varies, based on the tissue of origin. This case report describes a young woman who developed cutaneous EH with concurrent intracranial disease during pregnancy.

A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL).

Venous valve station changes in "primary" and postthrombotic reflux: an analysis of 149 cases.

The purpose of this study was to analyze valve station changes noted during venous valve reconstruction and the associated outcome. One hundred and forty-nine valve reconstructions were available for analysis at the time of surgical exploration; the venous valve was graded according to valve station changes (VS grades) from zero through six. Ascending venography was analyzed by a similar grading system and the two methods were compared.

Studies in calf venous pump function utilizing a two-valve experimental model.

Objectives: to explore the hydrodynamic mechanisms involved in the regulation of ambulatory venous pressure.

Design: an experimental model of calf venous pump was constructed with collapsible tubes and valves.

Material: the model consisted of a conduit and a pump with an intervening competent valve.

Saphenectomy in the presence of chronic venous obstruction.

Background: The results of saphenectomy in patients with morphologic and functional obstruction were compared with those in patients without obstruction. Excision of secondary saphenous varices associated with deep venous obstruction has long been considered contraindicated for fear of compromising its collateral contribution. Recent advances in accurate functional assessment of venous obstruction make it possible to test this concept.

Tube collapse and valve closure in ambulatory venous pressure regulation: studies with a mechanical model.

Purpose: To determine the role of valve closure and column segmentation in ambulatory venous pressure regulation.

Methods: Using a mechanical model consisting of a graduated adjustable valve and a collapsible tube, we studied the differential effects of valve closure and tube collapse on venous pressure regulation. By utilizing materials with differing wall properties for the infravalvular tube, the influence of wall property changes on tube function and pressure regulation was explored.

Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results.

We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal antibody that reacts with tenascin in gliomas/carcinomas but does not react with normal adult brain. 131I-labeled 81C6 delivers intrathecal (IT) radiation to these neoplasms.

Durability of venous valve reconstruction techniques for "primary" and postthrombotic reflux.

Purpose: The durability of the variety of valve reconstruction techniques in "primary" reflux and postthrombotic reflux was studied.

Methods: A total of 423 valve repairs in 235 patients with a follow-up period ranging from 1 to 12 years were analyzed. End points for assessment consisted of ulcer recurrence and Doppler competence in serial duplex examination.

Observations on the calf venous pump mechanism: determinants of postexercise pressure.

Purpose: We investigated the factors determining postexercise pressure and the relationship of venous valve closure and venous column segmentation to ambulatory venous pressure changes.

Methods: Valve closure and venous segmentation were observed during dynamic ascending phlebography in 40 nonrefluxive limbs and by duplex imaging in 25 normal limbs in healthy volunteers. Simultaneous volume (air plethysmography) and pressure studies during calf exercise were also carried out.

Cerebral vasculitis associated with cocaine abuse.

Background: Earlier reports of cocaine-associated cerebral vasculitis have been based primarily on angiographic findings without pathological verification.

Case Description: We present a case of acute encephalopathy following intravenous and intranasal administration of cocaine. Brain biopsy revealed vascular changes involving primarily small arteries.

Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations.

One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard.

Hemodynamic basis of stasis ulceration--a hypothesis.

Approximately 25% of patients with stasis ulceration have normal or below normal ambulatory venous pressures. A reflux index was calculated by multiplying postexercise pressures by Valsalva-induced foot venous pressure elevation. In patients with stasis ulceration, reflux index was found to have an excellent negative predictive value with a clear discriminant line between normal limbs and those with ulcers.