Successful Non-Invasive treatment of stricturing fibrosing colonopathy in an adult patient

<p>Abstract</p> <p>Objective</p> <p>Fibrosing colonopathy (FC) is a rare entity associated with cystic fibrosis (CF). Until now, patients with stricturing FC have usually been treated surgically. In this instance, we aimed at avoiding surgery by applying a new conservative approach.</p> <p>Methods</p> <p>Case report on an adult with CF who developed persistent abdominal pain due to a non-passable stricture in the right transverse colon. Histology confirmed fibrosing colonopathy.</p> <p>Results</p> <p>Initially we treated the patient with prednisolone pulse therapy and additive antibiotic therapy. For maintenance therapy we administered budesonide. The patient underwent clinical, laboratory and endoscopic follow-up over a three-year period. The stricture healed and was easy to pass. A relapse in the cecum at the ileocecal valve again improved under steroid and antibiotic therapy.</p> <p>Conclusions</p> <p>We present a novel therapeutic approach for advanced stricturing FC in an adult patient which successfully avoided surgery (right hemicolectomy) over a three year follow up.</p

Solution of the Multi-Channel Anderson Impurity Model: Ground state and thermodynamics

We present the solution of the SU(N) x SU(M) Anderson impurity model using the Bethe-Ansatz. We first explain what extensions to the formalism were required for the solution. Subsequently we determine the ground state and derive the thermodynamics over the full range of temperature and fields. We identify the different regimes of valence fluctuation at high temperatures, followed by moment formation or intrinsic mixed valence at intermediate temperatures and a low temperature non-Fermi liquid phase. Among other things we obtain the impurity entropy, charge valence and specific heat over the full range of temperature. We show that the low-energy physics is governed by a line of fixed points. This describes non-Fermi-liquid behavior in the integral valence regime, associated with moment formation, as well as in the mixed valence regime where no moment forms.Comment: 28 pages, 8 figures, 1 tabl

Quasiparticle Effective Mass for the Two- and Three-Dimensional Electron Gas

We calculate the quasiparticle effective mass for the electron gas in two and three dimensions in the metallic region. We employ the single particle scattering potential coming from the Sj\"{o}lander-Stott theory and enforce the Friedel sum rule by adjusting the effective electron mass in a scattering calculation. In 3D our effective mass is a monotonically decreasing function of $r_s$ throughout the whole metallic domain, as implied by the most recent numerical results. In 2D we obtain reasonable agreement with the experimental data, as well as with other calculations based on the Fermi liquid theory. We also present results of a variety of different treatments for the effective mass in 2D and 3D.Comment: 12 pages, 2 figure

The Influence of Social Evaluation on Heart Rate Variability and Motor Performance: A Study of “Real-Life” Competition

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Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study

Glaxo Wellcome Research and Development

Association of Locomotor Activity During Sleep Deprivation Treatment With Response

Disrupted circadian rhythms and sleep patterns are frequently observed features of psychiatric disorders, and especially mood disorders. Sleep deprivation treatment (SD) exerts rapid but transient antidepressant effects in depressed patients and has gained recognition as a model to study quick-acting antidepressant effects. It is of interest how locomotor activity patterns during SD might be associated with and potentially predict treatment response. The present study is an analysis of locomotor activity data, previously collected over a 24 h period, to examine the night of SD (Trautmann et al. 2018) as mood disorder patients suffering from a depressive episode (n = 78; after exclusions n = 59) underwent SD. In this exploratory analysis, the associations between response to SD, locomotor activity, and subjective mood during the 24 h period of SD were explored. Higher levels of activity overall were observed in non-responders (n = 18); in particular, non-responders moved more during the evening of SD until midnight and remained high thereafter. In contrast, activity in responders (n = 41) decreased during the evening and increased in the morning. Subjective mood was not found to be associated with locomotor activity. The window of data available in this analysis being limited, additional data from before and after the intervention are required to fully characterize the results observed. The present results hint at the possible utility of locomotor activity as a predictor and early indicator of treatment response, and suggest that the relationship between SD and locomotor activity patterns should be further investigated

Parity nonconserving cold neutron-parahydrogen interactions

Three pion dominated observables of the parity nonconserving interactions between the cold neutrons and parahydrogen are calculated. The transversely polarized neutron spin rotation, unpolarized neutron longitudinal polarization, and photon-asymmetry of the radiative polarized neutron capture are considered. For the numerical evaluation of the observables, the strong interactions are taken into account by the Reid93 potential and the parity nonconserving interactions by the DDH model along with the two-pion exchange.Comment: 17 pages, 2 figure

Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits

Private companies have begun offering services to allow parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This procedure, called polygenic embryo screening, raises several difficult scientific and ethical issues, as discussed in this Personal View. Polygenic embryo screening depends on the statistical properties of polygenic risk scores, which are complex and not well studied in the context of this proposed clinical application. The clinical, social, and ethical implications of polygenic embryo screening have barely been discussed among relevant stakeholders. To our knowledge, the International Society of Psychiatric Genetics is the first professional biomedical organisation to issue a statement regarding polygenic embryo screening. For the reasons discussed in this Personal View, the Society urges caution and calls for additional research and oversight on the use of polygenic embryo screening