The association between retinal vein ophthalmodynamometric force change and optic disc excavation

Aim: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic disc excavation in glaucoma, but it is not known if variation in ODF affects prognosis. We aimed to assess whether a change in ODF provides additional prognostic information. Methods: 135 eyes of 75 patients with glaucoma or being glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic disc photography and ODF measured on an initial visit and a subsequent visit at mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded on the latter visit. When venous pulsation was spontaneous, the ODF was recorded as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to determine the occurrence of optic disc excavation, which was modelled against the measured variables using multiple mixed effects logistic regression. Results: Change in ODF (p=0.046) was associated with increased excavation. Average IOP (p=0.66) and other variables were not associated. Odds ratio for increased optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was calculated. Conclusion: Change in retinal vein ODF may provide additional information to assist with glaucoma prognostication and implies a significant relationship between venous change and glaucoma patho-physiology

Discovery of Antagonist Peptides against Bacterial Helicase-Primase Interaction in B. stearothermophilus by Reverse Yeast Three-Hybrid

SummaryDeveloping small-molecule antagonists against protein-protein interactions will provide powerful tools for mechanistic/functional studies and the discovery of new antibacterials. We have developed a reverse yeast three-hybrid approach that allows high-throughput screening for antagonist peptides against essential protein-protein interactions. We have applied our methodology to the essential bacterial helicase-primase interaction in Bacillus stearothermophilus and isolated a unique antagonist peptide. This peptide binds to the primase, thus excluding the helicase and inhibiting an essential interaction in bacterial DNA replication. We provide proof of principle that our reverse yeast three-hybrid method is a powerful “one-step” screen tool for direct high-throughput antagonist peptide selection against any protein-protein interaction detectable by traditional yeast two-hybrid systems. Such peptides will provide useful “leads” for the development of new antibacterials

Reconsidering the nature and mode of action of metabolite retrograde signals from the chloroplast

Plant organelles produce retrograde signals to alter nuclear gene expression in order to coordinate their biogenesis, maintain homeostasis, or optimize their performance under adverse conditions. Many signals of different chemical nature have been described in the past decades, including chlorophyll intermediates, reactive oxygen species (ROS), and adenosine derivatives. While the effects of retrograde signaling on gene expression are well understood, the initiation and transport of the signals and their mode of action have either not been resolved, or are a matter of speculation. Moreover, retrograde signaling should be considered as part of a broader cellular network, instead of as separate pathways, required to adjust to changing physiologically relevant conditions. Here we summarize current plastid retrograde signaling models in plants, with a focus on new signaling pathways, SAL1-PAP, methylerythritol cyclodiphosphate (MEcPP), and β-cyclocitral (β-CC), and outline missing links or future areas of research that we believe need to be addressed to have a better understanding of plant intracellular signaling networks

Sustainability of physical exam skills in a resident-led curriculum in a large internal medicine program with competency based medical education

Background: Competency Based Medical Education (CBME) designates physical examination competency as an Entrustable Professional Activity (EPA). Considerable concern persists regarding the increased time burden CBME may place on educators. We developed a novel physical examination curriculum that shifted the burden of physical examination case preparation and performance assessment from faculty to residents. Our first objective was to determine if participation led to sustainable improvements in physical examination skills. The second objective was to determine if resident peer assessment was comparable to faculty assessment.    Methods: We selected physical exam case topics based on the Objectives of Training in the Specialty of Internal Medicine as prescribed by the Royal College of Physicians and Surgeons of Canada. Internal Medicine residents compiled evidence-based physical exam checklists that faculty reviewed before distribution to all learners. Physical exam practice sessions with whole-group demonstration followed by small-group practice sessions were performed weekly. We evaluated this pilot curriculum with a formative OSCE, during which a resident peer and a faculty member simultaneously observed and assessed examinee performance by .Results: Participation in the novel curriculum practice sessions improved OSCE performance (faculty score mean 78.96 vs. 62.50, p<0.05). Peer assessment overestimated faculty scores (76.2 vs. 65.7, p<0.001), but peer and faculty assessments were highly correlated (R2 = 0.73 (95% CI 0.50-0.87).Conclusion: This novel physical examination curriculum leads to sustainable improvement of physical examination skills. Peer assessment correlated well with the gold standard faculty assessment. This resident-led physical examination curriculum enhanced physical examination skills in a CBME environment, with minimal time commitment from faculty members

Less is more: a rationalization of daily labwork

Routine daily phlebotomy can often act as a replacement for direct patient care.  Some tests are necessary to gauge treatment response, however many are unnecessary and increase a patient’s risk of complications and can impede laboratory processing times. This study addresses the effects of providing resident trainees, who often lack an understanding of the financial impact of the tests they order, with summative feedback. This encouraged them to be resource-conscious. Internal Medicine teams were provided with weekly laboratory spending reports and this resulted in a 33% reduction in Per Person Per Day spending. No changes in mortality were noted

The Effects of Efficacy Framing in News Information and Health Anxiety on Coronavirus-Disease-2019-Related Cognitive Outcomes and Interpretation Bias

Within the coronavirus-disease-2019 (COVID-19) pandemic, disease-related information is omnipresent in the media, whereas information about how to manage the pandemic is less often covered. Under the context where threat is present, this study investigated whether and how the strength of efficacy framing (i.e., the perspective adopted by a communicating text that emphasizes one’s possibilities to cope with an external threat) of COVID-19-related news, as well as its interaction with trait health anxiety under the COVID-19 context, related to people’s COVID-19-related cognitive outcomes. One hundred and ninety-three participants reported demographics, trait health anxiety, and COVID-19-related behaviors (e.g., precautionary measures, information-seeking behaviors). They then either read high-efficacy (n = 112; e.g., cure rate) or low-efficacy (n = 81; e.g., mortality rate) information about COVID-19. Afterward, their tendency to interpret illness and COVID-19-related information more negatively, and other COVID-19-related cognitions (e.g., risk perception, behavioral change intentions) were assessed. High-efficacy framing resulted in lower-risk perception and marginally weaker COVID-19-related interpretation bias, compared with low-efficacy framing. There was some evidence of an interaction with health anxiety such that high-efficacy framing, compared with low-efficacy framing, was associated with greater intention to adopt protective behaviors, particularly for individuals with higher levels of health anxiety.</p

Development and analytical performance evaluation of an automated chemiluminescent immunoassay for pro-gastrin releasing peptide (ProGRP)

Background: Pro-gastrin releasing peptide ( ProGRP) concentrations in blood play an important role in the diagnosis and treatment of patients with small cell lung cancer (SCLC). The automated quantitative ARCHITECT (R) ProGRP assay was developed to aid in the differential diagnosis and in the management of SCLC. The purpose of this study was to evaluate the analytical performance of this chemiluminescent microparticle immunoassay at multiple sites. Methods: ARCHITECT ProGRP measures ProGRP using a two-step sandwich using monoclonal anti-ProGRP antibodies coated on paramagnetic microparticles and labeled with acridinium. Analytical performance of the assay was evaluated at four sites: Abbott Japan, Denka Seiken, the Johns Hopkins University, and the University of Munich. Results: Total precision (%CV) for nine analyte concentrations was between 2.2 and 5.7. The analytical sensitivity of the assay was between 0.20 pg/mL and 0.88 pg/mL. The functional sensitivity at 20% CV was between 0.66 pg/mL and 1.73 pg/mL. The assay was linear up to 50,000 pg/mL using a 1:10 autodilution protocol. The calibration curve was stable for 30 days. Comparison with the Fujirebio microtiter plate enzyme-linked immunosorbent assay (EIA) ProGRP assay gave a slope of 0.93 and a correlation coefficient (r) of 0.99. Conclusions: These results demonstrate that the ARCHITECT ProGRP assay has excellent sensitivity, precision, and correlation to a reference method. This assay provides a convenient automated method for ProGRP measurement in serum and plasma in hospitals and clinical laboratories. Clin Chem Lab Med 2009;47:1557-63