Development and validation of the Patient‐Physician Relationship Scale among patients with irritable bowel syndrome

BackgroundAn effective patient‐physician relationship (PPR) is essential to the care of patients with irritable bowel syndrome (IBS). We sought to develop and validate an IBS‐specific instrument to measure expectations of the PPR.MethodsWe conducted structured focus groups about PPRs with 12 patients with IBS. Qualitative analysis was used to generate a questionnaire (the Patient‐Physician Relationship Scale [PPRS]), which was modified with input from content experts and usability testing. For validation, we administered it online to US adults with IBS. Participants also completed the Functional Bowel Disorder Severity Index, the Rome III Adult Functional gastrointestinal (GI) Disorder Criteria Questionnaire, and modified versions of the Communication Assessment Tool (CAT‐15) and Patient‐Doctor Relationship Questionnaire (PDRQ‐9). We performed principal components factor analysis for the PPRS.Key ResultsThe PPRS contained 32 questions with responses on a 7‐item Likert scale. Themes included interpersonal features, clinical care expectations, and aspects of communication. One thousand and fifty‐four eligible individuals completed the survey (88% completion rate). Most participants were middle aged (mean 48 years, SD 16.3), white (90%), and female (86%). Factor analysis showed only one relevant factor, relating to quality of PPR. The final scale ranged from possible‐96 to +96 (mean 62.0, SD 37.6). It correlated moderately with the CAT‐15 (r=.40, P<.001) and PDRQ‐9 (r=.30, P<.001), establishing concurrent validity.Conclusions & InferencesWe describe the development and validation of the first questionnaire for use in measuring patient expectations of the PPR, which can be used for future outcomes studies and training physicians.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138227/1/nmo13106.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138227/2/nmo13106_am.pd

Membrane Recruitment of Scaffold Proteins Drives Specific Signaling

Cells must give the right response to each stimulus they receive. Scaffolding, a signaling process mediated by scaffold proteins, participates in the decoding of the cues by specifically directing signal transduction. The aim of this paper is to describe the molecular mechanisms of scaffolding, i.e. the principles by which scaffold proteins drive a specific response of the cell. Since similar scaffold proteins are found in many species, they evolved according to the purpose of each organism. This means they require adaptability. In the usual description of the mechanisms of scaffolding, scaffold proteins are considered as reactors where molecules involved in a cascade of reactions are simultaneously bound with the right orientation to meet and interact. This description is not realistic: (i) it is not verified by experiments and (ii) timing and orientation constraints make it complex which seems to contradict the required adaptability. A scaffold protein, Ste5, is used in the MAPK pathway of Saccharomyces Cerevisiae for the cell to provide a specific response to stimuli. The massive amount of data available for this pathway makes it ideal to investigate the actual mechanisms of scaffolding. Here, a complete treatment of the chemical reactions allows the computation of the distributions of all the proteins involved in the MAPK pathway when the cell receives various cues. These distributions are compared to several experimental results. It turns out that the molecular mechanisms of scaffolding are much simpler and more adaptable than previously thought in the reactor model. Scaffold proteins bind only one molecule at a time. Then, their membrane recruitment automatically drives specific, amplified and localized signal transductions. The mechanisms presented here, which explain how the membrane recruitment of a protein can produce a drastic change in the activity of cells, are generic and may be commonly used in many biological processes

Hydroimidazolone Modification of the Conserved Arg12 in Small Heat Shock Proteins: Studies on the Structure and Chaperone Function Using Mutant Mimics

Methylglyoxal (MGO) is an α-dicarbonyl compound present ubiquitously in the human body. MGO reacts with arginine residues in proteins and forms adducts such as hydroimidazolone and argpyrimidine in vivo. Previously, we showed that MGO-mediated modification of αA-crystallin increased its chaperone function. We identified MGO-modified arginine residues in αA-crystallin and found that replacing such arginine residues with alanine residues mimicked the effects of MGO on the chaperone function. Arginine 12 (R12) is a conserved amino acid residue in Hsp27 as well as αA- and αB-crystallin. When treated with MGO at or near physiological concentrations (2–10 µM), R12 was modified to hydroimidazolone in all three small heat shock proteins. In this study, we determined the effect of arginine substitution with alanine at position 12 (R12A to mimic MGO modification) on the structure and chaperone function of these proteins. Among the three proteins, the R12A mutation improved the chaperone function of only αA-crystallin. This enhancement in the chaperone function was accompanied by subtle changes in the tertiary structure, which increased the thermodynamic stability of αA-crystallin. This mutation induced the exposure of additional client protein binding sites on αA-crystallin. Altogether, our data suggest that MGO-modification of the conserved R12 in αA-crystallin to hydroimidazolone may play an important role in reducing protein aggregation in the lens during aging and cataract formation

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed