Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis

The pathogenesis of psoriasis is unknown, although it is generally accepted that this chronic inflammatory skin disorder is a complex autoimmune condition similar to other T-cell mediated disorders. Psoriasis imposes a heavy burden on the lifestyle of those affected due to the psychological, arthritic, and cutaneous morbidities; thus significant research has focused on the genetic and immunologic features of psoriasis in anticipation of more targeted, efficacious, and safe therapies. Recently, CD4+ T helper (Th) 17 cells and interleukins (IL)-12 and -23 have been important in the pathogenesis of T-cell mediated disorders such as psoriasis and has influenced the development of medications that specifically target these key immunological players. Ustekinumab is a monoclonal antibody belonging to a newly developed class of biological, anti-cytokine medications that notably targets the p40 subunit of both IL-12 and -23, both naturally occurring proteins that are important in regulating the immune system and are understood to play a role in immune-mediated inflammatory disorders. Ustekinumab’s safety and efficacy has been evaluated for the treatment of moderate-to-severe plaque psoriasis in 3 phase III clinical trials, 2 placebo-controlled (PHOENIX 1 and 2), and 1 comparator-controlled (ACCEPT) study which proved advantageous in patients who were treatment-naive, previously failed other immunosuppressive medications including cyclosporine or methotrexate, were unresponsive to phototherapy, or were unable to use or tolerate other therapies. Ustekinumab has also been investigated for other indications such as psoriatic arthritis, Crohn’s disease, and relapsing/remitting multiple sclerosis. We present a concise review evaluating the evidence that supports the use of ustekinumab in the treatment of plaque psoriasis and other conditions

Metal Anticancer Complexes - Activity, Mechanism of Action, Future Perspectives

Guest editors Enzo Alessio and Zijian Guo present an overview of the topics reported in the papers of this issue, listing the general trends that dominate the field of metal anticancer complexes. They provide an analysis of the development of this area of chemistry since its official start about 50 years ago, present the status quo and offer insights into future perspectives

External and intrinsic anchoring in nematic liquid crystals: A Monte Carlo study

We present a Monte Carlo study of external surface anchoring in nematic cells with partially disordered solid substrates, as well as of intrinsic anchoring at free nematic interfaces. The simulations are based on the simple hexagonal lattice model with a spatially anisotropic intermolecular potential. We estimate the corresponding extrapolation length $b$ by imposing an elastic deformation in a hybrid cell-like nematic sample. Our estimates for $b$ increase with increasing surface disorder and are essentially temperature--independent. Experimental values of $b$ are approached only when both the coupling of nematic molecules with the substrate and the anisotropy of nematic--nematic interactions are weak.Comment: Revisions primarily in section I

New Universality Class in three dimensions: the Antiferromagnetic RP2RP^2 model

We present the results of a Monte Carlo simulation of the $RP^2$ model in three dimensions with negative coupling. We observe a second order phase transition between the disordered phase and an antiferromagnetic, unfrustrated, ordered one. We measure, with a Finite Size Scaling analysis, the thermal exponent, obtaining $\nu=0.784(8)$. We have found two magnetic-type relevant operators whose related $\eta$ exponents are $0.038(2)$ and $1.338(8)$ respectively.Comment: 10 pages, 2 Postscript figures. Revised version: references adde

Statics and dynamics of the Lebwohl-Lasher model in the Bethe approximation

We study the Lebwohl-Lasher model for systems in which spin are arranged on random graph lattices. At equilibrium our analysis follows the theory of spin-systems on random graphs which allows us to derive exact bifurcation conditions for the phase diagram. We also study the dynamics of this model using a variant of the dynamical replica theory. Our results are tested against simulations.Comment: 16 pages, 5 eps figures, elsart; extended result

A Note on Non-equilibrium Work Fluctuations and Equilibrium Free Energies

We consider in this paper, a few important issues in non-equilibrium work fluctuations and their relations to equilibrium free energies. First we show that Jarzynski identity can be viewed as a cumulant expansion of work. For a switching process which is nearly quasistatic the work distribution is sharply peaked and Gaussian. We show analytically that dissipation given by average work minus reversible work $W_R$, decreases when the process becomes more and more quasistatic. Eventually, in the quasistatic reversible limit, the dissipation vanishes. However estimate of $p$ - the probability of violation of the second law given by the integral of the tail of the work distribution from $-\infty$ to $W_R$, increases and takes a value of $0.5$ in the quasistatic limit. We show this analytically employing Gaussian integrals given by error functions and Callen-Welton theorem that relates fluctuations to dissipation in process that is nearly quasistatic. Then we carry out Monte Carlo simulation of non-equilibrium processes in a liquid crystal system in the presence of an electric field and present results on reversible work, dissipation, probability of violation of the second law and distribution of workComment: 15 pages, 4 figure

Superconducting Plasma Excitation at Microwave Frequencies in Parallel Magnetic Fields in Bi2Sr2CaCu2O8+δ\mathrm{\mathbf{Bi_2Sr_2CaCu_2O_{8+\delta}}}

Josephson plasma resonance has been studied in a wide microwave frequency range between 10 and 52 GHz in a magnetic field parallel to the $ab$-plane in under-doped \BI. Above about 30 GHz two resonance modes were observed: one (LT mode) appears at low temperatures and another (HT mode) at higher temperatures, leaving a temperature gap between two regions. These two resonance modes exhibit a sharp contrast each other both on temperture and magnetic field dependences and show distinct characters different entirely from the c-axis Josephson plasma resonance. From temperature and field scan experiments at various frequencies it is suggested that the LT mode can be attributed to the coupled Josephson plasma mode with Josephson vortices, while the HT mode is a new plasma mode associated possibly with the periodic array of Josephson vortices.Comment: submitted to Physica C (Prceedings of Plasma2000, Sendai

Adverse events associated with colonoscopy; an examination of online concerns

Background Colonoscopy as a screening and diagnostic tool is generally safe and well-tolerated, and significant complications are rare. The rate of more mild adverse effects is difficult to estimate, particularly when such effects do not result in hospital admission. We aimed to identify the rate and timing of adverse effects as reported by users querying symptoms on an internet search engine. Methods We identified queries made to Bing originating from users in the United States containing the word “colonoscopy” during a 12-month period and identified those queries in which the timing of colonoscopy could be estimated. We then identified queries from those same users for medical symptoms during the time span from 5 days before through 30 days after the colonoscopy date. Results Of 641,223 users mentioning colonoscopy, 7013 (1.1%) had a query that enabled identification of their colonoscopy date. The majority of queries about colonoscopy preceded the procedure, and concerned diet. 28% of colonoscopy-related queries were made afterwards, and included queries about diarrhea and cramps, with 2.6% of users querying respiratory symptoms after the procedure, including cough (1.2%) and pneumonia (0.6%). Respiratory symptoms rose significantly at days 7–10 after the colonoscopy. Conclusions Internet search queries for respiratory symptoms rose approximately one week after queries relating to colonoscopy, raising the possibility that such symptoms are an under-reported late adverse effect of the procedure. Given the widespread use of colonoscopy as a screening modality and the rise of anesthesia-assisted colonoscopy in the United States in recent years, this signal is of potential public health concern