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( Theodore Pincus ),( Jacquelin R Chua ),( Kathryn A Gibson ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.4
Patient self-report questionnaires such as a multidimensional health assessment questionnaire (MDHAQ) have advanced knowledge concerning prognosis, care, course and outcomes of rheumatoid arthritis (RA). The MDHAQ may overcome some limitations of a “biomedical model,” the dominant paradigm of contemporary medical services, including limitations of laboratory tests, radiographs, joint counts, and clinical trials, to predict and depict the long-term course and outcomes of RA. A complementary “biopsychosocial model” captures components of a patient medical history on patient questionnaires as quantitative, standard, “scientific” scores for physical function, pain, fatigue, and other problems, rather than as “subjective” narrative descriptions. A rationale for a biopsychosocial model in RA includes the importance of a patient history in diagnosis and management compared to biomarkers in many chronic diseases such as hypertension and diabetes. Some important observations which support a biopsychosocial model in RA based on patient questionnaires include that MDHAQ physical function scores are far more significant than radiographs or laboratory tests to predict severe RA outcomes such as work disability and premature death; patient self-report measures are more efficient than tender joint counts and laboratory tests to distinguish active from control treatments in RA clinical trials involving biological agents; and MDHAQ scores are more likely than laboratory tests to be abnormal at presentation and to document incomplete responses to methotrexate at initiation of biological agents. Patient questionnaires can save time for doctors and patients, and improve doctor-patient communication. A standardized database of MDHAQ scores consecutive patients over long periods might be considered by all rheumatologists in routine clinical care. (J Rheum Dis 2016;23:212-233)
Liu, Lei,Pincus, Philip A.,Hyeon, Changbong American Chemical Society 2017 Macromolecules Vol.50 No.4
<P>Recent experiments have shown that trivalent ion, spermicline(3+), can provoke lateral microphase segregation in DNA brushes. Using molecular simulations and simple theoretical arguments, we explore the effects of trivalent counterions on polyelectrolyte brushes. At a proper range of grafting density, polymer size, and ion concentration, the brush polymers collapse heterogeneously into octopus-like surface micelles. Remarkably, the heterogeneity in brush morphology is maximized, and the relaxation dynamics of chain and condensed ion are the slowest at the 1:3 stoichiometric concentration of trivalent ions to polyelectrolyte charge. A further increase of trivalent ion concentration conducive to a charge inversion elicits modest reswelling and homogenizes the morphology of brush condensate. Our study provides a new insight into the origin of the diversity in DNA organization in cell nuclei as well as the ion-dependent morphological variation in polyelectrolyte brush layer of biological membranes.</P>
Effects of Dimethyl Sulfoxide on Surface Water near Phospholipid Bilayers
Lee, Yuno,Pincus, Philip A.,Hyeon, Changbong Published for the Biophysical Society by the Rocke 2016 Biophysical journal Vol.111 No.11
<P>Despite much effort to probe the properties of dimethyl sulfoxide (DMSO) solution, the effects of DMSO on water, especially near plasma membrane surfaces, still remain elusive. By performing molecular dynamics simulations at varying DMSO concentrations (X-DMSO), we study how DMSO affects structural and dynamical properties of water in the vicinity of phospholipid bilayers. As proposed by a number of experiments, our simulations confirm that DMSO induces dehydration from bilayer surfaces and disrupts the H-bond structure of water. However, DMSO-enhanced water diffusivity at solvent-bilayer interfaces, an intriguing discovery reported by a spin-label measurement, is not confirmed in our simulations. To resolve this discrepancy, we examine the location of the spin label (Tempo) relative to the solvent-bilayer interface. In accord with the evidence in the literature, our simulations, which explicitly model Tempo-phosphatidylcholine, find that the Tempo moiety is equilibrated at similar to 8-10 angstrom below the bilayer surface. Furthermore, the DMSO-enhanced surface-water diffusion is confirmed only when water diffusion is analyzed around the Tempo moiety that is immersed below the bilayer surface, which implies that the experimentally detected signal of water using Tempo stems from the interior of bilayers, not from the interface. Our analysis finds that the increase of water diffusion below the bilayer surface is coupled to the increase of area per lipid with an increasing XDMSO (less than or similar to 10 mol %). Underscoring the hydrophobic nature of the Tempo moiety, our study calls for careful re-evaluation of the use of Tempo in measurements on lipid bilayer surfaces.</P>
Electrostatic Interaction between Nonuniformly Charged Colloids: Experimental and Numerical Study
Derot, Claire,Porcar, Lionel,Lee, YongJin,Pincus, Phillip A.,Jho, YongSeok,In, Martin American Chemical Society 2015 Langmuir Vol.31 No.5
<P>The influence of the surface charge distribution on the interaction between nanosized particles in water is reported. The distribution of charges at the surface of initially neutral microemulsion droplets has been modulated by additions of various oligomeric cationic surfactants. The osmotic compressibility of the doped microemulsions was measured by light and small-angle neutrons scattering and reveals that the overall effective interaction induced by the ionic groups is repulsive. However, particular charge distributions decrease the osmotic compressibility much less than others. Independent measurements of the activity of the bromide counterions with specific electrodes evidence a significant decrease in the effective charge, which, however, cannot account for the osmotic compressibility in the framework of the primitive model. The <I>q</I> dependence of the structure factor reveals an attractive contribution over a short distance. Numerical studies assign this attractive contribution to the overlap of hydration shells that are extended as a result of the charge localization.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2015/langd5.2015.31.issue-5/la504579c/production/images/medium/la-2014-04579c_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la504579c'>ACS Electronic Supporting Info</A></P>
Alex van Belkum,Martin Welker,David Pincus,Jean-Philippe Charrier,Victoria Girard 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.6
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized the identification of microbial species in clinical microbiology laboratories. MALDI-TOF-MS has swiftly become the new gold-standard method owing to its key advantages of simplicity and robustness. However, as with all new methods, adoption of the MALDI-TOF MS approach is still not widespread. Optimal sample preparation has not yet been achieved for several applications, and there are continuing discussions on the need for improved database quality and the inclusion of additional microbial species. New applications such as in the field of antimicrobial susceptibility testing have been proposed but not yet translated to the level of ease and reproducibility that one should expect in routine diagnostic systems. Finally, during routine identification testing, unexpected results are regularly obtained, and the best methods for transmitting these results into clinical care are still evolving. We here discuss the success of MALDI-TOF MS in clinical microbiology and highlight fields of application that are still amenable to improvement.