Activity of CD101, a long-acting echinocandin,against clinical isolates of Candida auris

CD101 is a new echinocandin with a prolonged half-life. CD101 was tested by broth microdilution against 100 isolates of the emerging yeast Candida auris. It showed activity against most isolates, including some that were resistant to other echinocandins.     

Monkey visual behavior falls into the uncanny valley

Very realistic human-looking robots or computer avatars tend to elicit negative feelings in human observers. This phenomenon is known as the “uncanny valley” response. It is hypothesized that this uncanny feeling is because the realistic synthetic characters elicit the concept of “human,” but fail to live up to it. That is, this failure generates feelings of unease due to character traits falling outside the expected spectrum of everyday social experience. These unsettling emotions are thought to have an evolutionary origin, but tests of this hypothesis have not been forthcoming. To bridge this gap, we presented monkeys with unrealistic and realistic synthetic monkey faces, as well as real monkey faces, and measured whether they preferred looking at one type versus the others (using looking time as a measure of preference). To our surprise, monkey visual behavior fell into the uncanny valley: They looked longer at real faces and unrealistic synthetic faces than at realistic synthetic faces.     

13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS)

Cellular metabolism of glucose is required for stimulation of insulin secretion from pancreatic beta cells, but the precise metabolic coupling factors involved in this process are not known. In an effort to better understand mechanisms of fuel-mediated insulin secretion, we have adapted 13C NMR and isotopomer methods to measure influx of metabolic fuels into the tricarboxylic acid (TCA) cycle in insulinoma cells. Mitochondrial metabolism of [U-13C3]pyruvate, derived from [U-13C6]glucose, was compared in four clonal rat insulinoma cell 1-derived cell lines with varying degrees of glucose responsiveness. A 13C isotopomer analysis of glutamate isolated from these cells showed that the fraction of acetyl-CoA derived from [U-13C6]glucose was the same in all four cell lines (44 +/- 5%, 70 +/- 3%, and 84 +/- 4% with 3, 6, or 12 mM glucose, respectively). The 13C NMR spectra also demonstrated the existence of two compartmental pools of pyruvate, one that exchanges with TCA cycle intermediates and a second pool derived from [U-13C6]glucose that feeds acetyl-CoA into the TCA cycle. The 13C NMR spectra were consistent with a metabolic model where the two pyruvate pools do not randomly mix. Flux between the mitochondrial intermediates and the first pool of pyruvate (pyruvate cycling) varied in proportion to glucose responsiveness in the four cell lines. Furthermore, stimulation of pyruvate cycling with dimethylmalate or its inhibition with phenylacetic acid led to proportional changes in insulin secretion. These findings indicate that exchange of pyruvate with TCA cycle intermediates, rather than oxidation of pyruvate via acetyl-CoA, correlates with glucose-stimulated insulin secretion.     

Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting.

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.     

Resident recognition of open-angle glaucoma

To test an educational intervention’s effect on improving detection of glaucoma by direct ophthalmoscopy, 14 medicine residents examined five patients, two with ophthalmoscopic changes of glaucoma and three with normal fundi. The residents observed a standardized slide/narrative educational intervention reviewing glaucomatous ophthalmoscopic changes and then re-examined the same patients eight to 12 weeks later. The intervention’s odds of improving residents’ diagnostic impression were significant (OR=2.2; 95% CI=1.3–36), with significant improvement in sensitivity (p=0.02) and a trend toward improved specificity. These findings confirm that the diagnosis of glaucomatous ocular changes on eye examinations by medicine residents can be improved with a brief educational intervention. Presented in abstract form at the annual meeting of the Society of General Internal Medicine, Medical Education Section, April 29–May 1, 1992, Washington, DC, and at the Southern regional meeting of the Society of General Internal Medicine, Medical Education Section, January 29–31, 1992, New Orleans, Louisiana.     

Use and efficacy of pneumococcal vaccine in patients with Hodgkin disease.

Fulminant bacterial sepsis has been described in patients with Hodgkin disease who have undergone splenectomy for staging purposes. The organisms commonly associated with sepsis in this setting include Streptococcus pneumoniae and Haemophilus influenzae. Polyvalent pneumococcal vaccine (Merck) has recently been licensed and has been suggested for use in patients with Hodgkin disease who are at risk for postsplenectomy sepsis. We administered 14-valent pneumococcal vaccine to 24 patients with Hodgkin disease and 24 normal controls, and measured antibody response to 13 antigens at time of immunization and at 3 wk and 3 mo following immunization. Our results indicate that patients who have been previously treated for Hodgkin disease, with chemotherapy, radiotherapy, or both, have severe impairment of antibody response. Untreated patients, however, respond in a manner similar to normal controls.