The ion-activated attractive patchy particle model and its application to the liquid-vapor phase transitions.

Patchy particles are an intriguing subject of study and indeed a model system in the field of soft matter physics. In recent years, patchy particle models have been applied to describe a wide variety of systems, including colloidal crystals, macromolecular interactions, liquid crystals, and nanoparticle assemblies. Given the importance of the topic, rationalizing and capturing the basic features of these models is crucial to their correct application in specific systems. In this study, we extend the ion-activated attractive patchy particles model previously employed to elucidate the phase behavior of protein solutions in the presence of trivalent salts. Our extension incorporates the effect of repulsion between unoccupied and occupied binding sites, depicted as patches. Furthermore, we examine the influence of model parameters on the liquid-vapor coexistence region within the phase diagram, employing numerical methods. A deeper understanding of this model will facilitate a better comprehension of the effects observed in experiments.

An alternative approach to the osmotic second virial coefficient of protein solutions and its application to liquid-liquid phase separation.

The osmotic second virial coefficient B2 is an important parameter to describe the interactions and phase behavior of protein solutions, including colloidal systems and macromolecular solutions. Another key parameter to describe the driving force of the nucleation of a new phase is the supersaturation, which is used in the classical nucleation theory framework and is connected with the favorable contribution in the Gibbs free energy in the bulk solution. In this article, we establish a connection between B2 calculated from small angle x-ray scattering (SAXS) data and the values of B2 obtained from supersaturation measurements using thermodynamics considerations. The values of the second virial coefficient calculated employing this method agree with those determined via SAXS in the region near the liquid-liquid phase separation border for human serum albumin and bovine serum albumin. The general relations adopted are shown to be useful for the estimation of the second virial coefficient B2 for globular proteins, in the proximity of the binodal biphasic coexistent region.

Inside and out: Surface thermodynamics from positive to negative curvature.

To explore the curvature dependence of solid-fluid interfacial thermodynamics, we calculate, using Grand Canonical Monte Carlo simulation, the surface free energy for a 2d hard-disk fluid confined in a circular hard container of radius R as a function of the bulk packing fraction η and wall curvature C̄=-1/R. (The curvature is negative because the surface is concave.) Combining this with our previous data [Martin et al., J. Phys. Chem. B 124, 7938-7947 (2020)] for the positive curvature case (a hard-disk fluid at a circular wall, C̄=+1/R), we obtain a complete picture of surface thermodynamics in this system over the full range of positive and negative wall curvatures. Our results show that γ is linear in C̄ with a slope that is the same for both positive and negative wall curvatures, with deviations seen only at high negative curvatures (strong confinement) and high density. This observation indicates that the surface thermodynamics of this system is consistent with the predictions of so-called morphometric thermodynamics at both positive and negative curvatures. In addition, we show that classical density functional theory and a generalized scaled particle theory can be constructed that give excellent agreement with the simulation data over most of the range of curvatures and densities. For extremely high curvatures, where only one or two disks can occupy the container at maximum packing, it is possible to calculate γ exactly. In this limit, the simulations and density functional theory calculations are in remarkable agreement with the exact results.

Effects of Recurring IPC vs. rIPC Maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: Special Consideration of Reflow Varieties.

Beneficial effects of (remote) ischemia preconditioning ((r)IPC), short episodes of blood occlusion and reperfusion, are well-characterized, but there is no consensus regarding the effectiveness of (r)IPC on exercise performance. Additionally, direct comparisons of IPC and rIPC but also differences between reflow modes, low reflow (LR) and high reflow (HR) in particular, are lacking, which were thus the aims of this study. Thirty healthy males conducted a performance test before and after five consecutive days with either IPC or rIPC maneuvers (n = 15 per group). This procedure was repeated after a two-week wash-out phase to test for both reflow conditions in random order. Results revealed improved exercise parameters in the IPC LR and to a lesser extent in the rIPC LR intervention. RBC deformability increased during both rIPC LR and IPC LR, respectively. Pulse wave velocity (PWV) and blood pressures remained unaltered. In general, deformability and PWV positively correlated with performance parameters. In conclusion, occlusion of small areas seems insufficient to affect large remote muscle groups. The reflow condition might influence the effectiveness of the (r)IPC intervention, which might in part explain the inconsistent findings of previous investigations. Future studies should now focus on the underlying mechanisms to explain this finding.

Gas-liquid phase transition in a binary mixture with an interaction that creates constant density profiles.

If, in a hard sphere fluid, a single (test) particle is fixed, the other particles display a density profile that possesses long-ranged oscillations. Surprisingly, one can show via classical density functional theory that it takes a simple, purely repulsive (external) potential with a finite range in addition to the fixed hard sphere that forces these oscillations to vanish completely. This can give rise to interesting phenomena; however, it gained little attention in the past. In this work, we use the potential in question as an inter-component interaction in a binary hard-sphere mixture, where it is shown that the effective interaction induced by one component resembles qualitatively the well-known Asakura-Oosawa-Vrij potential and can lead to a liquid-gas phase transition in the other component.

Liquid-liquid phase separation in an inhomogeneous ternary colloid-polymer mixture.

Suspended colloids are often considered as models for molecules, which are sufficiently big so that they can be observed directly in (light) microscopes and for which the effective interaction among each other can be tailored. The Asakura-Oosawa model of ideal colloid-polymer mixtures captures the idea of tuning the interaction between the colloids via a potential, which possesses a range set by the size of the polymers and an attractive strength characterized by the (reservoir) number density of the polymers, which plays the role of an inverse temperature. The celebrated Asakura-Oosawa depletion potential allows one to recreate the bulk phase diagram of a simple fluid by employing a colloid-polymer mixture. This has been verified in theory, by computer simulations, and via experiments. Here, we study the phase behavior of a confined colloid-polymer mixture with two polymer species. The sizes and densities are chosen such that the resulting bulk phase diagram exhibits a second stable critical point within the framework of the classical density functional theory. Our results suggest that a suitably tuned colloid-polymer mixture can be an interesting model system to study fluids with two critical points.

Dynamical Density Functional Theory for the Drying and Stratification of Binary Colloidal Dispersions.

We develop a dynamical density functional theory based model for the drying of colloidal films on planar surfaces. We consider mixtures of two different sizes of hard-sphere colloids. Depending on the solvent evaporation rate and the initial concentrations of the two species, we observe varying degrees of stratification in the final dried films. Our model predicts the various structures described in the literature previously from experiments and computer simulations, in particular the small-on-top stratified films. Our model also includes the influence of adsorption of particles to the interfaces.

Statics and dynamics of a finite two-dimensional colloidal system with competing attractive critical Casimir and repulsive magnetic dipole interactions.

We continue our theoretical study of a recently proposed two-dimensional colloidal system with attractive critical Casimir and repulsive magnetic dipole forces that can be tuned easily and independently from each other via the temperature and the strength of an external magnetic field, respectively [K. Marolt, M. Zimmermann, and R. Roth, Phys. Rev. E 100, 052602 (2019)2470-004510.1103/PhysRevE.100.052602]. Using this freedom, it is possible to construct a competing interaction potential that causes microphase separation featuring spatially inhomogeneous cluster, stripe, and bubble phases in the bulk, i.e., in an infinite system without an external potential. In the present work, we demonstrate by means of density functional theory that microphase separation can also occur in finite geometries. In a square cell with a side length of 20 or 30 colloid diameters, we observe the emergence of highly structured cluster and ring phases at intermediate bulk densities in addition to almost uniform fluid phases for lower and higher bulk densities. We then employ dynamic density functional theory to determine how the system reacts when the temperature and the magnetic field are altered over time, and we show how to induce a transition from the liquid to the cluster/ring phase and also from the cluster directly to the ring phase. We find that often a slowly varying and nontrivial path in parameter space is required to reach a stable state, whereas abrupt changes are prone to lead to metastable configurations.

Low-intensity blood flow restriction calf muscle training leads to similar functional and structural adaptations than conventional low-load strength training: A randomized controlled trial.

The purpose of this study was to investigate whether a six-week, twice weekly resistance training (4 sets at 30% 1-RM until failure) with practical blood flow restriction (BFR) using 7cm wide cuffs with a twist lock placed below the patella is superior to training without BFR (NoBFR) concerning muscle mass and strength gains in calf muscles. A two-group (BFR n = 12, mean age 27.33 (7.0) years, training experience 7.3 (7.0) years; NoBFR n = 9, mean age 28.9 (7.4) years, training experience 7.1 (6.6) years) randomized matched pair design based on initial 1-RM was used to assess the effects on structural and functional adaptations in healthy males (Perometer calf volume [CV], gastrocnemius muscle thickness using ultrasound [MT], 7-maximal hopping test for leg stiffness [LS], 1-RM smith machine calf raise [1-RM], and visual analogue scale as a measure of pain intensity [VAS]). The mean number of repetitions completed per training session across the intervention period was higher in the NoBFR group compared to the BFR group (70 (16) vs. 52 (9), p = 0.002). VAS measured during the first session increased similarly in both groups from first to fourth set (p<0.001). No group effects or time×group interactions were found for CV, MT, LS, and 1-RM. However, there were significant time effects for MT (BFR +0.07 cm; NoBFR +0.04; p = 0.008), and 1-RM (BFR +40 kg; NoBFR +34 kg; p<0.001). LS and CV remained unchanged through training. VAS in both groups were similar, and BFR and NoBFR were equally effective for increasing 1-RM and MT in trained males. However, BFR was more time efficient, due to lesser repetition per training session.

Enhanced protein adsorption upon bulk phase separation.

In all areas related to protein adsorption, from medicine to biotechnology to heterogeneous nucleation, the question about its dominant forces and control arises. In this study, we used ellipsometry and quartz-crystal microbalance with dissipation (QCM-D), as well as density-functional theory (DFT) to obtain insight into the mechanism behind a wetting transition of a protein solution. We established that using multivalent ions in a net negatively charged globular protein solution (BSA) can either cause simple adsorption on a negatively charged interface, or a (diverging) wetting layer when approaching liquid-liquid phase separation (LLPS) by changing protein concentration (cp) or temperature (T). We observed that the water to protein ratio in the wetting layer is substantially larger compared to simple adsorption. In the corresponding theoretical model, we treated the proteins as limited-valence (patchy) particles and identified a wetting transition for this complex system. This wetting is driven by a bulk instability introduced by metastable LLPS exposed to an ion-activated attractive substrate.

Remnants of the disappearing critical point in chain-forming patchy fluids.

For a standard model of patchy colloidal fluids with patch number M = 2, where chain formation (polymerization) occurs, we show that Wertheim theory predicts critical behavior at vanishing density and temperature. The analysis is based on determining lines in the phase diagram of maximal correlation length and compressibility. Simulation studies identify the latter line and confirm our prediction of Fisher-Widom crossover, i.e., the asymptotic decay of the pair correlation function changes from monotonic to damped oscillatory as the density is increased. For M > 2, it is known that phase separation occurs with a true critical point. Our results support the notion that a "disappearing" critical point occurs in the limit M = 2 and we uncover its remnants.

Toward a density-functional theory for the Jagla fluid.

The so-called Jagla fluid is well known to exhibit, in addition to the usual gas-liquid critical point, also a liquid-liquid critical point, as well as a density anomaly. This makes it an interesting toy model for water, for which a liquid-liquid critical point is considered to exist but so far eludes experimental verification due to crystallization occurring in the corresponding metastable, deeply supercooled state. With the Jagla fluid being understood quite well in bulk-mostly via simulation studies-the focus of the present study is to describe the spatially inhomogeneous fluid in terms of classical density-functional theory (DFT) with the aim to be able to control its phase behavior on changing the shape or the nature of the confinement of the fluid. This information might contribute to guide potential experimental tests of the liquid-liquid critical point of actual water. We first determine the bulk phase diagram for the Jagla fluid by using thermodynamical perturbation theory. In doing so we explain why the perturbation theories of Barker and Henderson as well as of Weeks, Chandler, and Anderson fail to describe the Jagla fluid. We then continue to construct a perturbative DFT based on our bulk model, which shows significant improvement over the standard mean-field DFT valid at high temperatures. But ultimately the perturbative DFT breaks down at state points close to the binodal line and at low temperatures. This prevents us from achieving the original aim to study a highly confined, inhomogeneous Jagla fluid close to its liquid-liquid binodal.

Microphase separation in a two-dimensional colloidal system with competing attractive critical Casimir and repulsive magnetic dipole interactions.

We propose and study theoretically a colloidal system in two dimensions with attractive critical Casimir and repulsive magnetic dipole forces, wherein the strength of attraction and repulsion can be easily and independently tuned by adjusting the temperature and an external magnetic field, respectively. We expect this setup to be experimentally accessible and are confident that it can serve to deepen our understanding of the mechanisms behind microphase separation due to competing interactions. We develop a density functional theory for our model and present first results of our calculations in the form of a phase diagram for fixed temperature, but varying magnetic fields and bulk densities. For certain values of these parameters, we are able to confirm the existence of thermodynamically stable inhomogeneous density profiles in the bulk, such as parallel lamellar stripes, as well as clusters and voids on a hexagonal lattice.

On the decay of the pair correlation function and the line of vanishing excess isothermal compressibility in simple fluids.

We revisit the competition between attractive and repulsive interparticle forces in simple fluids and how this governs and connects the macroscopic phase behavior and structural properties, as manifested in pair correlation functions. We focus on the asymptotic decay of the total correlation function h(r) which is, in turn, controlled by the form of the pair direct correlation function c(r). The decay of rh(r) to zero can be exponential (monotonic) if attraction dominates repulsion and exponentially damped oscillatory otherwise. The Fisher-Widom (FW) line separates the phase diagram into two regions characterized by the two different types of asymptotic decays. We show that there is a new and physically intuitive thermodynamic criterion which approximates well the actual FW line. This new criterion defines a line where the isothermal compressibility takes its ideal gas value χT=χT id. We test our hypothesis by considering four commonly used models for simple fluids. In all cases, the new criterion yields a line in the phase diagram that is close to the actual FW line for the thermodynamic state points that are most relevant. We also investigate (Widom) lines of maximal correlation length, emphasizing the importance of distinguishing between the true and Ornstein-Zernike correlation lengths.

An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

OBJECTIVES: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally. METHODS: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed. RESULTS: An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses. CONCLUSIONS: The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice.

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

Morphometric Approach to Many-Body Correlations in Hard Spheres.

We model the thermodynamics of local structures within the hard sphere liquid at arbitrary volume fractions through the morphometric calculation of n-body correlations. We calculate absolute free energies of local geometric motifs in excellent quantitative agreement with molecular dynamics simulations across the liquid and supercooled liquid regimes. We find a bimodality in the density library of states where fivefold symmetric structures appear lower in free energy than fourfold symmetric structures and from a single reaction path predict a dynamical barrier which scales linearly in the compressibility factor. The method provides a new route to assess changes in the free energy landscape at volume fractions dynamically inaccessible to conventional techniques.

Type 2 diabetes mellitus and osteoarthritis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. METHODS: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. RESULTS: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. CONCLUSIONS: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues.

Many-body correlations from integral geometry.

In a recent letter we presented a framework for predicting the concentrations of many-particle local structures inside the bulk liquid as a route to assessing changes in the liquid approaching dynamical arrest. Central to this framework was the morphometric approach, a synthesis of integral geometry and liquid-state theory, which has traditionally been derived from fundamental measure theory. We present the morphometric approach in a new context as a generalization of scaled-particle theory, and we derive several morphometric theories for hard spheres of fundamental and practical interest. Our central result is a new theory that is particularly suited to the treatment of many-body correlation functions in the hard-sphere liquid, which we demonstrate by numerical tests against simulation.

Bulk structural information from density functionals for patchy particles.

We investigate bulk structural properties of tetravalent associating particles within the framework of classical density functional theory, building upon Wertheim's thermodynamic perturbation theory. To this end, we calculate density profiles within an effective test-particle geometry and compare to radial distribution functions obtained from computer simulations. We demonstrate that a modified version of the functional proposed by Yu and Wu [J. Chem. Phys. 116, 7094 (2002)] based on fundamental measure theory for hard spheres produces accurate results, although the functional does not satisfy the exactly known low-density limit. In addition, at low temperatures where particles start to form an amorphous tetrahedral network, quantitative differences between simulations and theory emerge due to the absence of geometrical information regarding the patch arrangement in the latter. Indeed, here we find that the theory fits better to simulations of the floating-bond model [E. Zaccarelli et al., J. Chem. Phys. 127, 174501 (2007)], which exhibits a weaker tetrahedral order due to more flexible bonds between particles. We also demonstrate that another common density functional approach by Segura et al. [Mol. Phys. 90, 759 (1997)] fails to capture fundamental structural properties.