Elucidating the mechanism of polymer/surfactant coacervate delivery/conditioning systems

For almost half a century, stimuli-responsive complexes formed by dilution of anionic surfactant/cationic polymer compositions have dominated conditioning shampoos and dilution-deposition delivery systems. There are a plethora of cationic polymers available but only a few are present in successful commercial products. Moreover, conditioning and delivery attributes are strongly dependent on compositional details and use conditions. In order to explore the reasons for the dominance of few polymers and the variability of performance with composition, we studied the effects on complex coacervate formation of polymer charge density and distribution, polymer backbone rigidity and hydrophilicity, and concentration relative to polymer overlap and entanglement concentrations and surfactant CMC by surface tensiometry, shear rheometry, and fluorescence spectroscopy. Our results show that, above the critical entanglement concentration, complex coacervates separate as shear-thinning gel networks that desorb anionic surfactant from the interface. Such networks are favored by polymers having relatively rigid hydrophilic backbones. Alternatively, systems below the critical overlap concentration separate as unconnected phase droplets which enhance interfacial adsorption. The importance of critical polymer concentrations on these delivery systems helps to provide a mechanistic scientific basis for better tailoring of compositions to confer optimal delivery of attributes

Doctor of Philosophy

dissertationLyme arthritis is the result of dysregulated immune response to infection by Borrelia burgdorferi, a tick-borne spirochete. Several immune modulators have been shown to be important to host defense and Lyme arthritis susceptibility, including toll- like receptor signaling, NF-kB activation, and various cytokines and chemokines, including type I IFN. Here we show that type I IFN and microRNAs play critical roles in modulating Lyme arthritis development. C3H mice exhibit an early, preclinical upregulation of type I IFN-responsive genes, which is associated with increased arthritis severity. Using C3H IFNAR -/- knockout mice, we showed that C3H mice lacking type I IFN signaling have a partial reduction in arthritis severity. Radiation chimeras showed that IFN signaling in both radiation sensitive and radiation resistant cells within the joint are required for maximal arthritis. Ex vivo cell sorting of cells isolated from joint tissue also showed that hematopoietic cells were the only cell types capable of initiating a type I IFN response after stimulation with B. burgdorferi, but both hematopoietic and resident cells were involved in amplification of the type I IFN response. Endothelial cells and fibroblasts were also major producers of IFN-responsive genes and inflammatory cytokines. MicroRNAs have been shown to be important immune regulators, and have been associated with several inflammatory diseases, including rheumatoid arthritis and lupus. Here we show that several microRNAs were differentially expressed in B6, C3H, and B6 IL10-/- mice infected with B. burgdorferi. MicroRNA-146a, a repressor of TLR signaling and NF-κB activation, was upregulated in all three strains, suggesting it plays an important role in the immune response to infection. B6 miR-146a-/- mice infected with B. burgdorferi developed more severe arthritis, had elevated myeloid infiltration, upregulation of inflammatory cytokines, and had fewer numbers of bacteria in joint tissue at 4 weeks postinfection, indicating that miR-146a-mediated regulation of NF-κB activation modulated immune response and arthritis development. Similar patterns of dysregulation were observed in B6 miR-146a -/- macrophages, which produced excessive cytokines, exhibited increased phagocytosis, and had elevated protein levels of TRAF6. Together, these data show that miR-146a is a critical regulator of NF-κB activation and arthritis development during infection with B. burgdorferi

Report of the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee of the HHS Tick Borne Disease Working Group

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by Borrelia burgdorferi, the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of the process, and provide recommendations as to how to best approach solutions that could lead to a better means to manage patients with persistent Lyme disease

Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius

quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and SogR1 (a LuxR homolog) interacts with OHHL to modulate transcription of specific target genes. and SOPE. and SOPE indicates the potential for neofunctionalization to occur during the process of genome degeneration

Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies

Background and Aims: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). Results: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. Conclusions: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC

Trial by jury in the United States

Th e Republic of Moldova is considering the adoption of trial by jury in select criminal cases. Th e following article is intended to contribute to the discussion of that proposal. Th e article will briefl y describe the history of juries under the English common law and as adopted by the United States. It will then outline some of the basic procedures in trials by jury as currently practiced in the United States federal court system

A Review of Recent Advances in the Polymeric Delivery of Attributes in Cosmetics and Personal Care Products

A multitude of polymers are used to deliver desired attributes to skin and hair in personal care products. This article reviews recent trends in the use of polymers to deliver personal care attributes. Precisely constructed block and graft copolymers widen the range of available mechanical properties and compatibilities. Hydrophobic stimuli responsive polymers can be triggered to become hydrophilic by changes in their environment and this can confer waterproof properties at low temperature and easy water removal at higher temperatures. Transfer-resistant cosmetics are derived from silicone resins. The structure/property relationships for rheology modifiers continue to be probed with surprising observations. Delivery systems for rinse-off products from complex coacervates have been extended to the delivery of colors and fragrances. Polymeric antimicrobials promise product preservation while minimizing the concern of skin permeation