Review of sociodemographic risk factors for presentation with advanced non-melanoma skin cancer.

PURPOSE: Non-melanoma skin cancers (NMSC) are often localized and associated with an excellent prognosis but a minority present with locally advanced or metastatic disease requiring extensive resection or systemic treatment. Medical factors that increase the risk of advanced skin cancers such as tobacco use, systemic immunosuppression or genetic syndromes have been described but the sociodemographic risk factors are relatively uninvestigated and under reported. In this review a cohort of patients presenting with periorbital NMSC is reviewed for social determinants of health correlated with presentation with advanced disease. METHODS: Patients presenting with periorbital NMSC during a 10-year period are categorized as advanced (those tumors requiring extensive local resection, sacrifice of the globe or systemic therapy) or non-advanced and demographic features are compared between the two groups. RESULTS: 274 cases of periorbital NMSC were classified as either non-advanced (177) or advanced (97). Patients with public safety net health insurance were twice as likely to present with advanced disease (25% vs 13%). Patients with advanced disease were significantly less likely to be under the care of a primary care physician, lived in economically depressed areas with lower mean household incomes, and lived further from tertiary medical care. CONCLUSION: Financial and sociodemographic features are strongly associated with presentation with advanced NMSC. Further work is needed to determine which sociodemographic features are independent risk factors. A better understanding of the relevant barriers to care may reduce the burden of advanced disease at presentation in the future.

Strategy updating mediated by specific retrosplenial-parafascicular-basal ganglia networks.

Adaptive behavior requires flexible control over learning and exploitation of potentially viable options. Within a particular task, careful learning of strategies that differ from the initially learned rule is especially important as it sets an individual's strategy repertoire. However, whether and how such strategy updating is mediated by specific brain networks has remained unclear. Retrosplenial cortex (RSC), a cortical area exhibiting extensive connectivity to dorso-medial striatum (DMS) and the hippocampal formation, has been broadly implicated in flexible learning and might be involved in strategy updating. Here, we investigate the specific role of mouse RSC in flexible learning, map relevant RSC-anchored cortico-thalamo-basal ganglia circuits, and dissect their role in strategy updating. Activity in RSC was neither required for initial rule learning nor to switch between previously learned rules but was specifically required to explore and learn new alternative options when previous ones were available but no longer appropriate. Such strategy updating depended on activity in RSC c-Fos+ ensembles associated with the original rule and on their connections to DMS and thalamic parafascicular nucleus (PF) neurons. At the circuit level, rule-related RSC projection neurons branched to innervate both DMS and PF neurons and mediated strategy updating through a RSC-DMS-substantia nigra reticulata (SNr)-PF network, coupling alternative exploration to outcome. In addition, a separate RSC-PF-RSC looped network promoted alternative exploration. Our results uncover cortico-basal ganglia-thalamo and cortico-thalamo networks involving subpopulations of neurons in RSC and PF that specifically control and implement strategy updating.

Managing Neuronal Ensembles: Somatostatin Interneuron Subpopulations Shape and Protect Cortical Neuronal Ensembles for Learning.

Learning is accompanied by temporal compression and sharpening of neuronal firing sequences. In this issue of Neuron, Adler et al. (2019), using a motor skill paradigm and its variant, uncover a dual role for somatostatin interneuron regulation to support ensemble compaction and protection in learning.

Highly Efficient Reusable Sponge-Type Catalyst Carriers Based on Short Electrospun Fibers.

This study reports on gold nanoparticles (AuNPs) immobilized in a sponge made of short electrospun fibers (Au-sponge), which show surprisingly high reaction rates at extremely low gold amount. Au-sponges are made by freeze-drying of dispersions of short electrospun fibers with preimmobilization of AuNPs. The resulting Au-sponges show very low densities around 7 mg cm-3 corresponding to a pore volume of about 150 mL g-1 , but low surface area and very low amount of AuNPs in the range of 0.29-3.56 wt%. In general, catalysts with immobilized AuNPs show much low reaction rates compared to systems with dispersed AuNPs. By contrast, the Au-sponge catalyst with immobilized AuNPs is discerned here as an extremely efficient catalyst even superior to other systems with dispersed AuNPs. The fidelity of the Au-sponges after reactions is good enough for manifold use and thereby provides a sustainable catalyst design as well.

Self-Organization of Gold Nanoparticle Assemblies with 3D Spatial Order and Their External Stimuli Responsiveness.

Gold nanoparticles (AuNP) with pyridyl end-capped polystyrenes (PS-4VP) as "quasi-monodentate" ligands self-assemble into ordered PS-4VP/AuNP nanostructures with 3D hexagonal spatial order in the dried solid state. The key for the formation of these ordered structures is the modulation of the ratio AuNP versus ligands, which proves the importance of ligand design and quantity for the preparation of novel ordered polymer/metal nanoparticle conjugates. Although the assemblies of PS-4VP/AuNP in dispersion lack in high dimensional order, strong plasmonic interactions are observed due to close contact of AuNP. Applying temperature as an external stimulus allows the reversible distortion of plasmonic interactions within the AuNP nanocomposite structures, which can be observed directly by naked eye. The modulation of the macroscopic optical properties accompanied by this structural distortion of plasmonic interaction opens up very interesting sensoric applications.

Polymer Cages as Universal Tools for the Precise Bottom-Up Synthesis of Metal Nanoparticles.

A template synthesis allows the preparation of monodisperse nanoparticles with high reproducibility and independent from self-assembly requirements. Tailor-made polymer cages were used for the preparation of nanoparticles, which were made of cross-linked macromolecules with pendant thiol groups. Gold nanoparticles (AuNPs) were prepared in the polymer cages in situ, by using different amounts of cages versus gold. The polymer cages exhibited a certain capacity, below which the AuNPs could be grown with excellent control over the size and shape. Control experiments with a linear diblock copolymer showed a continuous increase in the AuNP size as the gold feed increased. This completely different behavior regarding the AuNP size evolution was attributed to the flexibility of the polymer chain depending on cross-linking. Moreover, the polymer cages were suitable for the encapsulation of AgNPs, PdNPs, and PtNPs by the in situ method.

Polymer/Nanoparticle Hybrid Materials of Precise Dimensions by Size-Exclusive Fishing of Metal Nanoparticles.

Polymer cages prepared by etching of gold nanoparticles from polymer templates by the "grafting around" method are designed for selective separation of metal nanoparticles. The separation process is demonstrated as a fast biphasic ligand exchange reaction. The high separation efficiency and size selectivity of the polymer cage is verified by comparison with the linear block copolymer.

SorLA in glia: shared subcellular distribution patterns with caveolin-1.

SorLA is an established sorting and trafficking protein in neurons with demonstrated relevance to Alzheimer's disease (AD). It shares these roles with the caveolins, markers of membrane rafts microdomains. To further our knowledge on sorLA's expression and traffic, we studied sorLA expression in various cultured glia and its relation to caveolin-1 (cav-1), a caveolar microdomain marker. RT-PCR and immunoblots demonstrated sorLA expression in rat C6 glioma, primary cultures of rat astrocytes (PCRA), and human astrocytoma 1321N1 cells. PCRA were determined to express the highest levels of sorLA's message. Induction of differentiation of C6 cells into an astrocyte-like phenotype led to a significant decrease in sorLA's mRNA and protein expression. A set of complementary experimental approaches establish that sorLA and cav-1 directly or indirectly interact in glia: (1) co-fractionation in light-density membrane raft fractions of rat C6 glioma, PCRA, and human 1321N1 astrocytoma cells; (2) a subcellular co-localization distribution pattern in vesicular perinuclear compartments seen via confocal imaging in C6 and PCRA; (3) additional confocal analysis in C6 cells suggesting that the perinuclear compartments correspond to their co-localization in early endosomes and the trans-Golgi; and; (4) co-immunoprecipitation data strongly supporting their direct or indirect physical interaction. These findings further establish that sorLA is expressed in glia and that it shares its subcellular distribution pattern with cav-1. A direct or indirect cav-1/sorLA interaction could modify the trafficking and sorting functions of sorLA in glia and its proposed neuroprotective role in AD.