Adverse reactions of biological therapies in patients with psoriasis

Psoriasis is a chronic, immune-mediated disorder characterized by well demarcated, erythematous plaques covered by thick, silvery-white scales, most often located on the knees, elbows, sacral area and scalp. It has a significant impact on the patient\u27s quality of life. Biological therapies revolutionized the treatment of psoriasis vulgaris but there has been concern regarding the use of those agents due to severe adverse reactions reported in patients receiving TNF-α inhibitors for various inflammatory diseases. The aim of this paper is to review the most important adverse reactions reported in patients receiving biological treatments. The most common and severe side effects associated with biologicals are infections, cardiac adverse reactions, neurologic adverse reactions, lymphomas, non-melanoma skin cancers and hepatobiliary disease

Metachronal wave formation in a model of pulmonary cilia

A three-dimensional simulation of the formation of metachronal waves in rows of pulmonary cilia is presented. The cilia move in a two-layer fluid model. The fluid layer adjacent to the cilia bases is purely viscous while the tips of the cilia move through a viscoelastic fluid. An overlapping fixed-moving grid formulation is employed to capture the effect of the cilia on the surrounding fluid. In contrast with immersed boundary methods, this technique allows a natural enforcement of boundary conditions without the need for smoothing of singular force distributions. The fluid domains are discretized using a finite volume method. The 9 + 2 internal microtubule structure of an individual cilium is modeled using large-deflection, curved, finite-element beams. The microtubule skeleton is cross-linked to itself and to the cilium membrane through spring elements which model nexin links. The cilium membrane itself is considered to be elastic and subject to fluid stresses computed from the moving grid formulation as well as internal forces transmitted from the microtubule skeleton. A cilium is set into motion by the action of dynein molecules exerting forces between adjacent microtubules. Realistic models of the forces exerted by dynein molecules are extracted from measurements of observed cilia shapes

MOCVD-Fabricated TiO2 Thin Films: Influence of Growth Conditions on Fibroblast Cells Culture

TiO2 thin films with various morphologies were grown on Ti substrates by the LP-MOCVD technique (Low Pressure Chemical Vapour Deposition from Metal-Organic precursor), with titanium tetra-iso-propoxide as a precursor. All the films were prepared in the same conditions except the deposition time. They were characterized by X-ray diffraction, scanning electron microscopy, optical 15 interferometry, water contact angle measurements. MOCVD-fabricated TiO2 thin films are known to be adapted to cell culture for implant requirements. Human gingival fibroblasts were cultured on the various TiO2 deposits. Differences in cell viability (MTT tests) and cell spreading (qualitative assessment) were observed and related to film roughness, wettability and allotropic composition

A Laboratory Investigation of Supersonic Clumpy Flows: Experimental Design and Theoretical Analysis

We present a design for high energy density laboratory experiments studying the interaction of hypersonic shocks with a large number of inhomogeneities. These ``clumpy'' flows are relevant to a wide variety of astrophysical environments including the evolution of molecular clouds, outflows from young stars, Planetary Nebulae and Active Galactic Nuclei. The experiment consists of a strong shock (driven by a pulsed power machine or a high intensity laser) impinging on a region of randomly placed plastic rods. We discuss the goals of the specific design and how they are met by specific choices of target components. An adaptive mesh refinement hydrodynamic code is used to analyze the design and establish a predictive baseline for the experiments. The simulations confirm the effectiveness of the design in terms of articulating the differences between shocks propagating through smooth and clumpy environments. In particular, we find significant differences between the shock propagation speeds in a clumpy medium compared to a smooth one with the same average density. The simulation results are of general interest for foams in both inertial confinement fusion and laboratory astrophysics studies. Our results highlight the danger of using average properties of inhomogeneous astrophysical environments when comparing timescales for critical processes such as shock crossing and gravitational collapse times.Comment: 7 pages, 6 figures. Submitted to the Astrophysical Journal. For additional information, including simulation animations and the pdf and ps files of the paper with embedded high-quality images, see http://pas.rochester.edu/~wm

In vitro bio-functional performances of the novel superelastic beta-type Ti-23Nb-0.7Ta-2Zr-0.5N alloy

International audienceThe materials used for internal fracture fixations and joint replacements are mainly made of metals which still face problems ranging from higher rigidity than that of natural bone to leaching cytotoxic metallic ions. Beta (β)-type titanium alloys with low elastic modulus made from non-toxic and non-allergenic elements are desirable to reduce stress shielding effect and enhance bone remodeling. In this work, a new β-type Ti-23Nb-0.7Ta-2Zr-0.5N alloy with a Young's modulus of approximately 50 GPa was designed and characterized. The behavior of MC3T3-E1 pre-osteoblasts on the new alloy, including adhesion, proliferation and differentiation, was evaluated by examining the cytoskeleton, focal adhesion formation, metabolic activity and extracellular matrix mineralization. Results indicated that the pre-osteoblast cells exhibited a similar degree of attachment and growth on Ti-23Nb-0.7Ta-2Zr-0.5N and Ti-6Al-4V. However, the novel alloy proved to be significantly more efficient in sustaining mineralized matrix deposition upon osteogenic induction of the cells than Ti-6Al-4V control. Further, analysis of RAW 264.7 macrophages cytokine gene and protein expression indicated no significant inflammatory response. Collectively, these findings suggest that the Ti-23Nb-0.7Ta-2Zr-0.5N alloy, which has an increased mechanical biocompatibility with bone, allows a better osteogenic differentiation of osteoblast precursor cells than Ti-6Al-4V and holds great potential for future clinical prosthetic applications

The Virtual Pediatric Airways Workbench

The Virtual Pediatric Airways Workbench (VPAW) is a patient-centered surgical planning software system targeted to pediatric patients with airway obstruction. VPAW provides an intuitive surgical planning interface for clinicians and supports quantitative analysis regarding prospective surgeries to aid clinicians deciding on potential surgical intervention. VPAW enables a full surgical planning pipeline, including importing DICOM images, segmenting the airway, interactive 3D editing of airway geometries to express potential surgical treatment planning options, and creating input files for offline geometric analysis and computational fluid dynamics simulations for evaluation of surgical outcomes. In this paper, we describe the VPAW system and its use in one case study with a clinician to successfully describe an intended surgery outcome

Extensions of the Ferry shear wave model for active linear and nonlinear microrheology

The classical oscillatory shear wave model of Ferry et al. [J. Polym. Sci. 2:593-611, (1947)] is extended for active linear and nonlinear microrheology. In the Ferry protocol, oscillation and attenuation lengths of the shear wave measured from strobe photographs determine storage and loss moduli at each frequency of plate oscillation. The microliter volumes typical in biology require modifications of experimental method and theory. Microbead tracking replaces strobe photographs. Reflection from the top boundary yields counterpropagating modes which are modeled here for linear and nonlinear viscoelastic constitutive laws. Furthermore, bulk imposed strain is easily controlled, and we explore the onset of normal stress generation and shear thinning using nonlinear viscoelastic models. For this paper, we present the theory, exact linear and nonlinear solutions where possible, and simulation tools more generally. We then illustrate errors in inverse characterization by application of the Ferry formulas, due to both suppression of wave reflection and nonlinearity, even if there were no experimental error. This shear wave method presents an active and nonlinear analog of the two-point microrheology of Crocker et al. [Phys. Rev. Lett. 85: 888 - 891 (2000)]. Nonlocal (spatially extended) deformations and stresses are propagated through a small volume sample, on wavelengths long relative to bead size. The setup is ideal for exploration of nonlinear threshold behavior

Spatial stress and strain distributions of viscoelastic layers in oscillatory shear

One of the standard experimental probes of a viscoelastic material is to measure the response of a layer trapped between parallel surfaces, imposing either periodic stress or strain at one boundary and measuring the other. The relative phase between stress and strain yields solid-like and liquid-like properties, called the storage and loss moduli, respectively, which are then captured over a range of imposed frequencies. Rarely are the full spatial distributions of shear and normal stresses considered, primarily because they cannot be measured except at boundaries and the information was not deemed of particular interest in theoretical studies. Likewise, strain distributions throughout the layer were traditionally ignored except in a classical protocol of Ferry, Adler and Sawyer, based on snapshots of standing shear waves. Recent investigations of thin lung mucus layers exposed to oscillatory stress (breathing) and strain (coordinated cilia), however, suggest that the wide range of healthy conditions and environmental or disease assaults lead to conditions that are quite disparate from the “surface loading” and “gap loading” conditions that characterize classical rheometers. In this article, we extend our previous linear and nonlinear models of boundary stresses in controlled oscillatory strain to the entire layer. To illustrate non-intuitive heterogeneous responses, we characterize experimental conditions and material parameter ranges where the maximum stresses migrate into the channel interior

Improving the lens design and performance of a contemporary electromagnetic shock wave lithotripter

Electromagnetic (EM) shock wave lithotripters are widely used for noninvasive treatment of kidney stone patients. Here, we report the design of a new acoustic lens to rectify three fundamental drawbacks in contemporary EM lithotripters, based on in situ pulse superposition, leading to significantly improved stone comminution both in vitro and in vivo with minimal tissue injury. The new lens design improves the pressure distribution around the lithotripter focus with better alignment of the peak pressure and cavitation activities with the kidney stones under clinically relevant treatment conditions. The general principle of the new lens design is applicable to different lenses or reflectors and with further optimizations may enhance the performance and safety of contemporary EM lithotripters