Characterizing the protein corona of sub-10 nm nanoparticles.

Studies into the interactions of serum proteins with nanoparticles are typically performed using nanoparticles that are larger than the size of proteins. Due to this size discrepancy, adsorbed proteins are commonly depicted as a globular structure surrounding a nanoparticle. Here, we asked how we should view nanoparticle-protein complexes when the nanoparticles are of similar size or smaller than the proteins with which they interact. We showed that nanoparticles can serve as a cargo on a protein rather than as a carrier of the protein in a size-dependent manner. This can occur when nanoparticles are below 10 nm in diameter. We discovered that when the nanoparticle is a cargo on the protein, the binding of the protein to the receptor target is minimally affected in contrast to the nanoparticle serving as a carrier. Our study should change how we view and describe nanoparticle-protein complexes when the nanoparticles involved are equal in size or smaller than proteins.

Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues.

The role of tissue architecture in mediating nanoparticle transport, targeting, and biological effects is unknown due to the lack of tools for imaging nanomaterials in whole organs. Here, we developed a rapid optical mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput electrophoretic flow device to simultaneously transform up to 48 tissues into optically transparent structures, allowing subcellular imaging of nanomaterials more than 1 mm deep into tissues which is 25-fold greater than current techniques. A key finding is that nanomaterials can be retained in the processed tissue by chemical cross-linking of surface adsorbed serum proteins to the tissue matrix, which enables nanomaterials to be imaged with respect to cells, blood vessels, and other structures. We developed a computational algorithm to analyze and quantitatively map nanomaterial distribution. This method can be universally applied to visualize the distribution and interactions of materials in whole tissues and animals including such applications as the imaging of nanomaterials, tissue engineered constructs, and biosensors within their intact biological environment.

DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction.

Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

Interventions to reduce the consequences of stress in physicians: a review and meta-analysis.

A significant proportion of physicians and medical trainees experience stress-related anxiety and burnout resulting in increased absenteeism and disability, decreased patient satisfaction, and increased rates of medical errors. A review and meta-analysis was conducted to examine the effectiveness of interventions aimed at addressing stress, anxiety, and burnout in physicians and medical trainees. Twelve studies involving 1034 participants were included in three meta-analyses. Cognitive, behavioral, and mindfulness interventions were associated with decreased symptoms of anxiety in physicians (standard differences in means [SDM], -1.07; 95% confidence interval [CI], -1.39 to -0.74) and medical students (SDM, -0.55; 95% CI, -0.74 to -0.36). Interventions incorporating psychoeducation, interpersonal communication, and mindfulness meditation were associated with decreased burnout in physicians (SDM, -0.38; 95% CI, -0.49 to -0.26). Results from this review and meta-analysis provide support that cognitive, behavioral, and mindfulness-based approaches are effective in reducing stress in medical students and practicing physicians. There is emerging evidence that these models may also contribute to lower levels of burnout in physicians.

Interventions to reduce stress in university students: a review and meta-analysis.

BACKGROUND: Recent research has revealed concerning rates of anxiety and depression among university students. Nevertheless, only a small percentage of these students receive treatment from university health services. Universities are thus challenged with instituting preventative programs that address student stress and reduce resultant anxiety and depression. METHOD: A systematic review of the literature and meta-analysis was conducted to examine the effectiveness of interventions aimed at reducing stress in university students. Studies were eligible for inclusion if the assignment of study participants to experimental or control groups was by random allocation or parallel cohort design. RESULTS: Retrieved studies represented a variety of intervention approaches with students in a broad range of programs and disciplines. Twenty-four studies, involving 1431 students were included in the meta-analysis. Cognitive, behavioral and mindfulness interventions were associated with decreased symptoms of anxiety. Secondary outcomes included lower levels of depression and cortisol. LIMITATIONS: Included studies were limited to those published in peer reviewed journals. These studies over-represent interventions with female students in Western countries. Studies on some types of interventions such as psycho-educational and arts based interventions did not have sufficient data for inclusion in the meta-analysis. CONCLUSION: This review provides evidence that cognitive, behavioral, and mindfulness interventions are effective in reducing stress in university students. Universities are encouraged to make such programs widely available to students. In addition however, future work should focus on developing stress reduction programs that attract male students and address their needs.

Pax7 expressing cells contribute to dermal wound repair, regulating scar size through a ß-catenin mediated process.

During skin wound healing, fibroblast-like cells reconstitute the dermal compartment of the repaired skin filling the wound gap. A subset of these cells are transcriptionally active for ß-catenin/T-cell factor (TCF) signaling during the proliferative phase of the repair process, and ß-catenin levels control the size of the scar that ultimately forms by regulating the number of dermal fibroblasts. Here, we performed cell lineage studies to reveal a source of the dermal cells in which ß-catenin signaling is activated during wound repair. Using a reporter mouse, we found that cells in the early wound in which TCF-dependent transcription is activated express genes involved in muscle development. Using mice in which cells express Pax7 (muscle progenitors) or Mck (differentiated myocytes) are permanently labeled, we showed that one quarter of dermal cells in the healing wound are Pax7 expressing progeny, but none are Mck progeny. Removing one allele of ß-catenin in Pax7 expressing progeny resulted in a significantly smaller scar size with fewer Pax7 expressing progeny cell contributing to wound repair. During wound healing, ß-catenin activation causes muscle satellite cells to adopt a fibrotic phenotype and this is a source of dermal cells in the repair process.

The case that has psychiatrists running scared: Ahmed v. Stefaniu.

In the three decades since the definitive decisions regarding duty to warn and protect, several cases have shaped psychiatric practice. In this article we present a tragic case that we postulate may have a significant effect on psychiatric practice in Canada. A psychiatric patient murdered a relative some 50 days after the patient left the hospital. On the day before his release, the patient's status was changed from involuntary to voluntary. We argue that this case may result in a reversal of current mental health and social policy, whereby psychiatrists will be less willing to release difficult and potentially dangerous patients. To provide context to the case, we review some concepts of the literature and recent legal cases pertaining to the release of such patients.