Features of heterogeneously charged systems at their liquid-liquid critical point.

Recently synthesized colloids and biological systems such as proteins, viruses and monoclonal antibodies are heterogeneously charged, i.e., different regions of their surfaces carry different amounts of positive or negative charge. Because of charge inhomogeneity, electrostatic interactions between these units through the surrounding medium are intrinsically anisotropic, meaning that they are characterized not only by the attraction between oppositely charged regions but also by the repulsion between like-charged areas. Recent experiments have shown that the liquid-liquid phase separation of these systems can be driven by anisotropic electrostatic interactions, but it is not clear how the emerging aggregates are affected by charge imbalance and charge patchiness. The ability to experimentally control these two quantities calls for a theoretical understanding of their interplay, which we address here at the critical point. We consider a coarse-grained model of anisotropically charged hard spheres whose interaction potential is grounded in a robust mean field theory and perform extensive numerical Monte Carlo simulations to understand the aggregation behavior of these units at the critical point. Stemming from the simplicity of the model, we address the interplay between charge imbalance and charge patchiness with the use of three parameters only and fully rationalize how these features impact the critical point of the model by means of thermodynamic-independent pair properties.

Hierarchical self-assembly of patchy colloidal platelets.

Anisotropy at the level of the inter-particle interaction provides the particles with specific instructions for the self-assembly of target structures. The ability to synthesize non-spherical colloids, together with the possibility of controlling the particle bonding pattern via suitably placed interaction sites, is nowadays enlarging the playing field for materials design. We consider a model of anisotropic colloidal platelets with regular rhombic shape and two attractive sites placed along adjacent edges and we run Monte Carlo simulations in two-dimensions to investigate the two-stage assembly of these units into clusters with well-defined symmetries and, subsequently, into extended lattices. Our focus is on how the site positioning and site-site attraction strength can be tuned to obtain micellar aggregates that are robust enough to successively undergo to a second-stage assembly from sparse clusters into a stable hexagonal lattice.

Design of Patchy Rhombi: From Close-Packed Tilings to Open Lattices.

In the realm of functional materials, the production of two-dimensional structures with tunable porosity is of paramount relevance for many practical applications: surfaces with regular arrays of pores can be used for selective adsorption or immobilization of guest units that are complementary in shape and/or size to the pores, thus achieving, for instance, selective filtering or well-defined responses to external stimuli. The principles that govern the formation of such structures are valid at both the molecular and the colloidal scale. Here we provide simple design directions to combine the anisotropic shape of the building units-either molecules or colloids-and selective directional bonding. Using extensive computer simulations, we show that regular rhombic platelets decorated with attractive and repulsive interaction sites form specific tilings, going smoothly from close-packed arrangements to open lattices. The rationale behind the rich tiling scenario observed can be described in terms of steric incompatibilities, unsatisfied bonding geometries, and interplays between local and long-range order.

A Matter of Size and Placement: Varying the Patch Size of Anisotropic Patchy Colloids.

Non-spherical colloids provided with well-defined bonding sites-often referred to as patches-are increasingly attracting the attention of materials scientists due to their ability to spontaneously assemble into tunable surface structures. The emergence of two-dimensional patterns with well-defined architectures is often controlled by the properties of the self-assembling building blocks, which can be either colloidal particles at the nano- and micro-scale or even molecules and macromolecules. In particular, the interplay between the particle shape and the patch topology gives rise to a plethora of tilings, from close-packed to porous monolayers with pores of tunable shapes and sizes. The control over the resulting surface structures is provided by the directionality of the bonding mechanism, which mostly relies on the selective nature of the patches. In the present contribution, we investigate the effect of the patch size on the assembly of a class of anisotropic patchy colloids-namely, rhombic platelets with four identical patches placed in different arrangements along the particle edges. Larger patches are expected to enhance the bond flexibility, while simultaneously reducing the bond selectivity as the single bond per patch condition-which would guarantee a straightforward mapping between local bonding arrangements and long-range pattern formation-is not always enforced. We find that the non-trivial interplay between the patch size and the patch position can either promote a parallel particle arrangement with respect to a non-parallel bonding scenario or give rise to a variety a bonded patterns, which destroy the order of the tilings. We rationalize the occurrence of these two different regimes in terms of single versus multiple bonds between pairs of particles and/or patches.

Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Tuning the order of colloidal monolayers: assembly of heterogeneously charged colloids close to a patterned substrate.

We study the behavior of negatively charged colloids with two positively charged polar caps close to a planar patterned surface. The competition between the different anisotropic components of the particle-particle interaction is able by itself to give rise to a rich assembly scenario: colloids with charged surface patterns already form different crystalline domains when adsorbed to a homogeneously charged substrate. Here we consider substrates composed of alternating (negative/neutral, positive/neutral and positive/negative) parallel stripes and, by means of Monte Carlo simulations, we investigate the ordering of the colloids on changing the number of the stripes. We show that the additional competition between the two different lengths scales characterizing the system (i.e., the particle interaction range and the size of the stripes) gives rise to a plethora of distinct particle arrangements, where some well-defined trends can be observed. By accurately tuning the substrate charged motif it is possible to, e.g., promote specific particle arrangements, disfavor crystalline domains or induce the formation of extended, open clusters.

Molecular dynamics simulations of inverse patchy colloids.

Inverse patchy colloids are patchy particles with differently charged surface regions. In this paper we focus on inverse patchy colloids with two different polar patches and an oppositely charged equatorial belt, and we describe a model and a reliable and efficient numerical algorithm that can be applied to investigate the properties of these particles in molecular dynamics simulations.

Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Limiting the valence: advancements and new perspectives on patchy colloids, soft functionalized nanoparticles and biomolecules.

Limited bonding valence, usually accompanied by well-defined directional interactions and selective bonding mechanisms, is nowadays considered among the key ingredients to create complex structures with tailored properties: even though isotropically interacting units already guarantee access to a vast range of functional materials, anisotropic interactions can provide extra instructions to steer the assembly of specific architectures. The anisotropy of effective interactions gives rise to a wealth of self-assembled structures both in the realm of suitably synthesized nano- and micro-sized building blocks and in nature, where the isotropy of interactions is often a zero-th order description of the complicated reality. In this review, we span a vast range of systems characterized by limited bonding valence, from patchy colloids of new generation to polymer-based functionalized nanoparticles, DNA-based systems and proteins, and describe how the interaction patterns of the single building blocks can be designed to tailor the properties of the target final structures.

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.