Biodegradable,Drug‐Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics

The stabilization and transport of low‐solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self‐assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)‐block‐poly(trimethylene carbonate), synthesized via organocatalyzed ring‐opening polymerization, undergo assembly into highly uniform, drug‐loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug‐loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).     

Natural occurrence of bisphenol F in mustard

Bisphenol F (BPF) was found in mustard up to a concentration of around 8 mg kg^?1. Contamination of the raw products or caused by the packaging could be ruled out. Also, the fact that only the 4,4?-isomer of BPF was detected spoke against contamination from epoxy resin or other sources where technical BPF is used. Only mild mustard made of the seeds of Sinapis alba contained BPF. In all probability BPF is a reaction product from the breakdown of the glucosinolate glucosinalbin with 4-hydroxybenzyl alcohol as an important intermediate. Hot mustard made only from brown mustard seeds (Brassica juncea) or black mustard seeds (Brassica nigra) contained no BPF. BPF is structurally very similar to bisphenol A and has a similar weak estrogenic activity. The consumption of a portion of 20 g of mustard can lead to an intake of 100–200 µg of BPF. According to a preliminary risk assessment, the risk of BPF in mustard for the health of consumers is considered to be low, but available toxicological data are insufficient for a conclusive evaluation. It is a new and surprising finding that BPF is a natural food ingredient and that this is the main uptake route. This insight sheds new light on the risk linked to the family of bisphenols.     

Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro

In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.     

Rubber-modified epoxies: III. Influence of the rubber molecular weight on the phase separation process

The effect of varying the rubber molecular weight on the reaction induced phase separation taking place in rubber-modified epoxies is reported. Three butadiene–acrylonitrile copolymers with number-average molecular weights of 2030, 3600 and 6050 g mol^?1 were used. The thermosetting polymer was an epoxy based on diglycidylether of bisphenol-A cured with a cycloaliphatic diamine. Increasing the rubber molecular weight showed the following effects: (i) a decrease in the conversion at the cloud point; (ii) a corresponding decrease in the viscosity at the cloud point; (iii) a primary morphology of a low concentration of particles with a large size; (iv) a more complete segregation of the rubber from the matrix leading to a smaller decrease of the glass transition temperature of the system; (v) a decrease in the toughening. The Flory–Huggins lattice model may be used as a simple approximation to describe the phase separation process when varying the rubber molecular weight.     

World benevolence beliefs and well-being across the life span.

Do people's worldviews change across the life course? Beliefs in the benevolence (goodness) of the world and their relations with age and well-being were examined in a 2-year study of a nationally representative sample (N = 2,138) ranging in age from 18 to 101 years. Multilevel modeling analyses controlling for demographics, mental health history, prior experience with stressful life events, and other key beliefs indicated that benevolence beliefs were positively associated with well-being and that these associations were stronger with increasing age. Analyses also demonstrated that individuals' benevolence beliefs increased during the study, were positively associated with age, and increased with the experience of bereavement, although they declined with the experience of other negative events. Age-related worldview change may be a part of life-span adaptation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Convergent validy of the Agnew Relationship Measure and the Working Alliance Inventory.

The convergent validity of the Agnew Relationship Measure (ARM) and the Working Alliance Inventory (WAI) was assessed in samples drawn from 2 comparative clinical trials of time-limited psychotherapies for depression. In 1 sample, clients (n=18) and therapists (n=4) completed self-report versions of both measures after every session (n=198). In the other sample, clients (n=39) and therapists (n=6) completed the ARM, and observers subsequently rated selected audiotaped sessions (n=78) using the WAI. In both samples, the ARM's core alliance scales (Bond, Partnership, and Confidence) were correlated with the WAI's scales (Bond, Tasks, and Goals) strongly when assessed within client and therapist perspectives and, with some qualifications, moderately when assessed between client, therapist, and observer perspectives, supporting the assumption that the ARM and the WAI measure some of the same core constructs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Review of Les fondements de la psychologie sociale, 2e édition.

Reviews the book, Les fondements de la psychologie sociale, 2e édition edited by Robert J. Vallerand (2006). Social psychology is a fascinating field of research. It enables us to explain collective phenomena as well as interpersonal behaviors and group dynamics. Robert J. Vallerand proposes an exciting scientific voyage into the heart of human social behaviors, constantly stressing the psychological mechanisms which manage them. The scientific contribution of this book is singular; it was it in its first edition and remains with this one a "must" for whoever is interested in social psychology. The foundations of social psychology can definitively and without any doubt be classified as a "classic". (PsycINFO Database Record (c) 2010 APA, all rights reserved)