Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives.

Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increased risk of serious infections, malignancy, and laboratory abnormalities. There is currently a large armamentarium of therapies for psoriatic arthritis, and choosing among treatments can be challenging. Due to this wide selection, a thorough assessment of psoriatic disease phenotype, patient preference, disease presentation, and comorbidities is critical. This review addresses key considerations in patient selection for the treatment of PsA with tofacitinib

Early Neolithic Wine of Georgia in the South Caucasus

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics from sites in Georgia in the South Caucasus region, dating to the early Neolithic period (ca. 6,000–5,000 BC), provide the earliest biomolecular archaeological evidence for grape wine and viniculture from the Near East, at ca. 6,000–5,800 BC. The chemical findings are corroborated by climatic and environmental reconstruction, together with archaeobotanical evidence, including grape pollen, starch, and epidermal remains associated with a jar of similar type and date. The very large-capacity jars, some of the earliest pottery made in the Near East, probably served as combination fermentation, aging, and serving vessels. They are the most numerous pottery type at many sites comprising the so-called “Shulaveri-Shomutepe Culture” of the Neolithic period, which extends into western Azerbaijan and northern Armenia. The discovery of early sixth millennium BC grape wine in this region is crucial to the later history of wine in Europe and the rest of the world

Aberrant Disgust Responses and Immune Reactivity in Cocaine-Dependent Men

Background: Infectious diseases are the most common and cost-intensive health complications associated with drug addiction. There is wide belief that drug-dependent individuals expose themselves more regularly to disease-related pathogens through risky behaviors such as sharing pipes and needles, thereby increasing their risk for contracting an infectious disease. However, evidence is emerging indicating that not only lifestyle but also the immunomodulatory effects of addictive drugs, such as cocaine, may account for their high infection risk. As feelings of disgust are thought to be an important psychological mechanism in avoiding the exposure to pathogens, we sought to investigate behavioral, physiological, and immune responses to disgust-evoking cues in both cocaine-dependent and healthy men. Methods: All participants (N = 61) were exposed to neutral and disgust-evoking photographs depicting food and nonfood images while response accuracy, latency, and skin conductivity were recorded. Saliva samples were collected before and after exposure to neutral and disgusting images, respectively. Attitudes toward disgust and hygiene behaviors were assessed using questionnaire measures. Results: Response times to disgust-evoking photographs were prolonged in all participants, and specifically in cocaine-dependent individuals. While viewing the disgusting images, cocaine-dependent individuals exhibited aberrant skin conductivity and increased the secretion of the salivary cytokine interleukin-6 relative to control participants. Conclusion: Our data provide evidence of a hypersensitivity to disgusting stimuli in cocaine-dependent individuals, possibly reflecting conditioned responses to noningestive sources of infection. Coupled with a lack of interoception of bodily signals, aberrant disgust responses might lead to increased infection susceptibility in affected individuals

The Radial Structure of SNR N103B

We report on the results from a Chandra ACIS observation of the young, compact, supernova remnant N103B. The unprecedented spatial resolution of Chandra reveals sub-arcsecond structure, both in the brightness and in spectral variations. Underlying these small-scale variations is a surprisingly simple radial structure in the equivalent widths of the strong Si and S emission lines. We investigate these radial variations through spatially resolved spectroscopy using a plane-parallel, non-equilibrium ionization model with multiple components. The majority of the emission arises from components with a temperature of 1 keV: a fully ionized hydrogen component; a high ionization timescale (n_e*t > 10^12 s cm^-3) component containing Si, S, Ar, Ca, and Fe; and a low ionization timescale (n_e*t ~ 10^{11} s cm^-3) O, Ne, and Mg component. To reproduce the strong Fe Kalpha line, it is necessary to include additional Fe in a hot (> 2 keV), low ionization (n_e*t ~ 10^10.8 s cm^-3) component. This hot Fe may be in the form of hot Fe bubbles, formed in the radioactive decay of clumps of 56Ni. We find no radial variation in the ionization timescales or temperatures of the various components. Rather, the Si and S equivalent widths increase at large radii because these lines, as well as those of Ar and Ca, are formed in a shell occupying the outer half of the remnant. A shell of hot Fe is located interior to this, but there is a large region of overlap between these two shells. In the inner 30% of the remnant, there is a core of cooler, 1 keV Fe. We find that the distribution of the ejecta and the yields of the intermediate mass species are consistent with model prediction for Type Ia events.Comment: 34 pages, including 7 tables and 7 figures, Accepted by Ap

Chronic pain:a review of its epidemiology and associated factors in population-based studies

Chronic pain is a common, complex, and distressing problem that has a profound impact on individuals and society. It frequently presents as a result of a disease or an injury; however, it is not merely an accompanying symptom, but rather a separate condition in its own right, with its own medical definition and taxonomy. Studying the distribution and determinants of chronic pain allows us to understand and manage the problem at the individual and population levels. Targeted and appropriate prevention and management strategies need to take into account the biological, psychological, socio-demographic, and lifestyle determinants and outcomes of pain. We present a narrative review of the current understanding of these factors.</p

Interleukin-10 (IL-10) but not Lipopolysaccharide (LPS) produces increased motor activity and abnormal exploratory patterns while impairing spatial learning in Balb/c mice

Lipopolysaccharide (LPS) is a potent endotoxin, which produces âsickness behavioursâ including loss of weight, loss of interest in food and decreased exploration. LPS has also been shown in some studies to cause deficits in various learning and memory abilities, while in others these LPS-induced learning impairments have been attributed to performance-related deficits rather than learning deficits per se. Here, we use the novelty-preference paradigm, a task that minimises performance-related factors such as motivation, in an attempt to extract and examine the effects of LPS on spatial learning. In addition, some studies have indicated that the anti-inflammatory cytokine Interleukin-10 (IL-10) can alleviate some of the symptoms induced by LPS. Here, we also examine the effect of IL-10 on feeding, motor and learning behaviours. We demonstrate that a single injection of LPS does produce a lack of interest in food and weight loss; LPS, however, does not impair habituation in the noveltypreference paradigm. Furthermore, co-injection of IL-10 with LPS does not attenuate the LPS-induced effects of weight loss and lack of food intake. Interestingly, a single injection of IL-10 produces abnormal patterns of exploration, a general increase in activity and abnormal patterns of habituation

Exploring the Fate of Nitrogen Heterocycles in Complex Prebiotic Mixtures

A long standing question in the field of prebiotic chemistry is the origin of the genetic macromolecules DNA and RNA. DNA and RNA have very complex structures with repeating subunits of nucleotides, which are composed of nucleobases (nitrogen heterocycles) connected to sugar-phosphate. Due to the instability of some nucleobases (e.g. cytosine), difficulty of synthesis and instability of D-ribose, and the likely scarcity of polyphosphates necessary for the modern nucleotides, alternative nucleotides have been proposed for constructing the first genetic material. Thus, we have begun to investigate the chemistry of nitrogen heterocycles in plausible, complex prebiotic mixtures in an effort to identify robust reactions and potential alternative nucleotides. We have taken a complex prebiotic mixture produced by a spark discharge acting on a gas mixture of N2, CO2, CH4, and H2, and reacted it with four nitrogen heterocycles: uracil, 5-hydroxymethyluracil, guanine, and isoxanthopterin (2-amino-4,7-dihydroxypteridine). The products of the reaction between the spark mixture and each nitrogen heterocycle were characterized by liquid chromatography coupled to UV spectroscopy and Orbitrap mass spectrometry. We found that the reaction between the spark mixtUl'e and isoxanthopterin formed one major product, which was a cyanide adduct. 5-hydroxymethyluracil also reacted with the spark mixture to form a cyanide adduct, uracil-5-acetonitrile, which has been synthesized previously by reacting HCN with S-hydroxymethyluracil. Unlike isoxanthopterin, the chromatogram of the 5-hydroxymethyluracil reaction was much more complex with multiple products including spark-modified dimers. Additionally, we observed that HMU readily self-polymerizes in solution to a variety of oligomers consistent with those suggested by Cleaves. Guanine and uracil, the biological nucleobases, did not react with the spark mixture, even at high temperature (100 C). This suggests that there are alternative nucleobases which are more reactive under prebiotic conditions and may have been involved in producing precursor nucleotides

Penguin decays of B mesons

Penguin, or loop, decays of B mesons induce effective flavor-changing neutral currents, which are forbidden at tree level in the Standard Model. These decays give special insight into the CKM matrix and are sensitive to non-standard model effects. In this review, we give a historical and theoretical introduction to penguins and a description of the various types of penguin processes: electromagnetic, electroweak, and gluonic. We review the experimental searches for penguin decays, including the measurements of the electromagnetic penguins b -> s gamma and B -> K* gamma and gluonic penguins B -> K pi, B+ -> omega K+ and B -> eta' K, and their implications for the Standard Model and New Physics. We conclude by exploring the future prospects for penguin physics.Comment: 49 pages, LATEX, 30 embedded figures, submitted to Annual Reviews of Nuclear and Particle Scienc