Amyloid formation: interface influence

The causes of pathological conditions such as Alzheimer’s and Parkinson’s diseases are becoming better understood. Proteins that misfold from their native structure to form aggregates of β-sheet fibrils — termed amyloid — are known1,2 to be implicated in these ‘amyloid diseases’. Understanding the early steps of fibril formation is critical, and the conditions, mechanism and kinetics of protein and peptide aggregation are being widely investigated through a variety of in vitro studies. Kinetic aspects of the dispersion of the protein or peptide in solution are thought to influence the fibrillization process by mass-transfer effects. In addition, mixing also leads to shear forces, which can influence fibril growth by perturbing the equilibrium between the isolated and aggregated proteins, causing existing fibrils to fragment and create new nuclei3. Writing in the Journal of the American Chemical Society, David Talaga and co-workers have now highlighted4 an additional factor that can influence the fibrillization of amyloid-forming proteins — the presence of hydrophobic interfaces

Oral medicine acceptance in infants and toddlers: measurement properties of the caregiver-administered Children’s acceptance tool (CareCAT)

BACKGROUND: Developing age-appropriate medications remains a challenge in particular for the population of infants and toddlers, as they are not able to reliably self-report if they would accept and consequently take an oral medicine. Therefore, it is common to use caregivers as proxies when assessing medicine acceptance. The outcome measures used in this research field differ and most importantly lack validation, implying a persisting gap in knowledge and controversy in the field. The newly developed Caregiver-administered Children’s Acceptance Tool (CareCAT) is based on a 5-point nominal scale, with descriptors of medication acceptance behavior. This crosssectional study assessed the measurement properties of the tool with regards to the user’s understanding and its intra- and inter-rater reliability. METHODS: Participating caregivers were enrolled at a primary healthcare facility where their children (median age 6 months) had been prescribed oral antibiotics. Caregivers, trained observers and the tool developer observed and scored on the CareCAT tool what behavior children exhibited when receiving the medicine (n = 104). The videorecords of this process served as replicate observations (n = 69). After using the tool caregivers were asked to explain their observations and the tool descriptors in their own words. The tool’s reliability was assessed by percentage agreement and Cohen’s unweighted kappa coefficients of agreement for nominal scales. RESULTS: The study found that caregivers using CareCAT had a satisfactory understanding of the tool’s descriptors. Using its dichotomized scores the tool reliably was strong for acceptance behavior (agreement inter-rater 84–88%, kappa 0.66–0.76; intra-rater 87–89%, kappa 0.68–0.72) and completeness of medicine ingestion (agreement inter-rater 82–86%, kappa 0.59–0.67; intra-rater 85–93%, kappa 0.50–0.70). CONCLUSIONS: The CareCAT is a low-cost, easy-to-use and reliable instrument, which is relevant to assess acceptance behavior and completeness of medicine ingestion, both of which are of significant importance for developing age-appropriate medications in infants and toddlers

Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide

This paper describes studies of a series of macrocyclic β-sheet peptides 1 that inhibit the aggregation of a tau-protein-derived peptide. The macrocyclic β-sheet peptides comprise a pentapeptide "upper" strand, two δ-linked ornithine turn units, and a "lower" strand comprising two additional residues and the β-sheet peptidomimetic template "Hao". The tau-derived peptide Ac-VQIVYK-NH(2) (AcPHF6) aggregates in solution through β-sheet interactions to form straight and twisted filaments similar to those formed by tau protein in Alzheimer's neurofibrillary tangles. Macrocycles 1 containing the pentapeptide VQIVY in the "upper" strand delay and suppress the onset of aggregation of the AcPHF6 peptide. Inhibition is particularly pronounced in macrocycles 1a, 1d, and 1f, in which the two residues in the "lower" strand provide a pattern of hydrophobicity and hydrophilicity that matches that of the pentapeptide "upper" strand. Inhibition varies strongly with the concentration of these macrocycles, suggesting that it is cooperative. Macrocycle 1b containing the pentapeptide QIVYK shows little inhibition, suggesting the possibility of a preferred direction of growth of AcPHF6 β-sheets. On the basis of these studies, a model is proposed in which the AcPHF6 amyloid grows as a layered pair of β-sheets and in which growth is blocked by a pair of macrocycles that cap the growing paired hydrogen-bonding edges. This model provides a provocative and appealing target for future inhibitor design

Emergency department presentation of an unusual pleural effusion.

Pleural effusion as a manifestation of malignancy is commonly encountered in clinical practice; most are transudates or exudates of endogenous body fluids. We report a case of pleural effusion that is directly related to the inadvertent infusion of chemotherapeutic agents into the hemithorax of a patient with ovarian carcinoma. With the increasingly common use of outpatient intravenous therapy, emergency department presentations of unusual pleural effusions should be considered

Chlorine inhalation: the big picture.

BACKGROUND: Causes of acute chlorine exposures from community pool accidents have many reported etiologies. This case series involves 13 children exposed to high levels of chlorine at two community pools after an unusual mishap in the chlorination maintenance procedure. CASE REPORT: During maintenance, the water feeding lines to pools are normally turned off, the chemicals replaced, the water turned back on, and the chemicals then reinjected into the line. In two separate disasters in the summer of 1996, the feeding lines were not reprimed with water before the reactants, sodium hypochlorite and muriatic acid, were injected. This caused an unusually high volume of concentrated chlorinated water to be released when refed to the pool. RESULTS: All patients were treated with beta agonists and humidified oxygen, and five were admitted. None received bicarbonate inhalation. An extensive literature review of chlorine inhalation injuries indicates considerable variance in opinions of the pathophysiology, clinical presentation and treatment modalities, especially steroids and bicarbonate inhalation. CONCLUSION: In community pools, failure to reprime feeding lines with water after replacing and injecting chlorinating reactants may result in severe and large-scale chlorine exposures. Beta agonist administration and humidified oxygen remains the mainstay of treatment; steroid therapy and bicarbonate inhalation are still inadequately supported

Does wearing a necktie influence patient perceptions of emergency department care?

We conducted a prospective study of discharged emergency department (ED) patients to determine the effect of wearing a necktie by emergency physicians (EPs) had on patients\u27 impression of their medical care. All male EPs were assigned randomly by dates to wear a necktie or no necktie, and the attire worn was otherwise similar in all respects. The study was conducted at a community teaching hospital with an Emergency Medicine residency and an annual census of 40,000. A total of 316 patients were surveyed. There were no statistically significant differences between patient groups in any of the five areas surveyed, including patient perception of physicians\u27 appearance. Nearly 30% of patients incorrectly identified their doctor as wearing a necktie when no necktie was worn, and the perception of tie wearing was correlated with a positive impression of physician appearance. Wearing or not wearing a necktie did not significantly affect patients\u27 impression of their physician or the care they received. However, patients seemingly preferred the appearance of physicians who were perceived to wear neckties

Impact of emergency medicine residents on ancillary test utilization.

The effect of the addition of emergency medicine residency on the use of ancillary testing in a teaching hospital\u27s emergency department (ED) staffed previously by emergency medicine board-certified physicians was studied. Prospectively, the utilization of three common ancillary tests (electrolyte levels, X-ray, or electrocardiogram) for four common chief complaints of patients eventually discharged from the ED was evaluated. A 12-month period before and a 15-month period after introduction of an emergency medicine residency program were compared. The mean number of ancillary tests utilized by the ED attending physicians working with residents was compared with the mean number of tests generated by the same physicians (all emergency medicine board-certified) for the same complaints in the year before the residents\u27 arrival. There was no significant difference in test use before and after introduction of the residency (P = .66). Faculty use of tests was also unaffected by the concurrent presence of residents (P = .068). These results show that the use of testing for a sample of common ED complaints was not affected by the introduction of emergency medicine residents to a previously emergency medicine board-certified staff in one community teaching hospital

Paramedic interpretation of prehospital lead-II ST-segments.

OBJECTIVE: To determine the reliability of ST-segment interpretation by paramedics from lead-II rhythm strips obtained in the prehospital setting. DESIGN: Prospective, blinded study of 127 patients transported by an urban/rural emergency medical services system with complaints consistent with ischemic heart disease. METHODS: Emergency department physicians asked emergency medical technician-paramedics (EMT-P) via radio to evaluate ST-segments for elevation or depression and grade it as mild, moderate, or severe. Then, this rhythm strip was interpreted blindly by emergency physicians who also interpreted the lead-II obtained from a 12-lead electrocardiogram (ECG) obtained in the emergency department (ED). The field interpretation was compared with the subsequent readings and the final in-patient diagnosis using positive predictive value (PPV), negative predictive value (NPV), and the Kappa statistic. Markedly discrepant interpretations were analyzed separately. RESULTS: Using physician interpretation as the reference standard, paramedic interpretation of the lead-II ST-segments obtained in the prehospital setting was correct (within +/- 1 gradation) in 113 out of 127 total cases (89%). Of 105 patients for whom final hospital diagnosis was available, the ST-segment on the rhythm strip obtained in the prehospital setting, had a positive predictive value of 74% and a negative predictive value of 85% for myocardial ischemia or myocardial infarction (MI) (p \u3c 0.001, Kappa = 0.59). Discordant interpretations between the paramedics and emergency physicians often were related to a basic misunderstanding of rhythm strip morphology. CONCLUSION: Field interpretation of ST-segments by paramedics is fairly accurate as judged both by emergency physicians and correlation with final patient outcome, but its clinical utility is unproved. A small but clinically significant number of outliers, consisting of markedly discrepant false positives, reflects paramedic uncertainty in identifying the deviations of the ST-segment