Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men

We compared the effect of vortioxetine, paroxetine and placebo after three days of dosing on sleep architecture. This was a randomised, double-blind, four-way crossover, placebo-controlled, multiple-dose study in 24 healthy young men. Subjects received 20mg vortioxetine, 40mg vortioxetine, 20mg paroxetine or placebo for three consecutive days in four different periods with at least three weeks between them. Polysomnography and blood sampling for pharmacokinetic analysis were performed on the pre-dose night and nights 1 and 3 of dosing in each period. Plasma concentrations of vortioxetine and paroxetine during the polysomnography measurement were used to estimate SERT occupancies using published relationships in healthy subjects. All three active treatments significantly increased REM onset latency and decreased time spent in REM sleep. In the pharmacokinetic/pharmacodynamics analysis significant relationships were found between REM onset latency and time spent in REM sleep and vortioxetine/paroxetine exposure. The relation between REM suppression parameters and SERT occupancy was significantly different between vortioxetine and paroxetine, despite the same SERT occupancy. This indicates that vortioxetine has a different clinical pharmacological profile from paroxetine, which may explain the differences in adverse effect profile of the two drugs, for instance the lower incidence of nausea, weight gain and sexual dysfunction with vortioxetine

Accuracy in evaluation of view factors between small and far surfaces

The contribution describes an approach that can be used during evaluation of a view factor between complex emitter and planar absorber surfaces. Rather than sophisticated mathematical attitude, practical way is offered. The source surface is divided into smaller parts with same surface normal and using some minor assumptions, summary view factor is calculated. The contribution is aimed on an error that can be caused considering these assumptions and further on, on a case study (evaluation of a view factor between ceramic plaques source surface and a photometric sensor), real differences are shown

On the relation between shape and downward radiation of overhead radiant heaters

The paper aims on evaluating and assessing of the influence of a shape of overhead luminous infrared heater’s burner on heat distribution to the ambient. These devices are mainly used for heating of industrial or other large space buildings. The contribution is based on comparison between the experimental results and created mathematical model. The latest experimental results show that the maximum of radiant intensity does not lay right below the radiant heater. Actually, there exists a ring of maximal values around heater’s midpoint axis. Results prove that instead of reflectors’ geometry, very complicated shape of gas luminous heater’s burner plays the most significant role in radiant heat transfer from the luminous heater. It was evaluated that the position of the radiant intensity maximum is around 10° from the radiating surface’s normal direction. All the findings can be summarized in conclusion that uniform distribution of radiant intensity required for thermal comfort of occupants can be maintained just by optimizing of the shape of radiant heater’s burner. Besides this conclusion, it is also apparent that adding the reflector actually increases summary radiant heat flux to the desired zone and therefore radiant efficiency increases. It is also clear that varying the reflector shape, different improvement of the efficiency can be expected

Design optimization study for an infrared heater using CFD and sensitivity analysis

Sensitivity analysis (SA) has become a very popular technique for various application areas. However, not many studies concern SA using CFD (computational fluid dynamics). The main problem appears to be the large number of model executions when using the Monte Carlo method of SA. The computing resources and time needed for such a SA in combination with CFD (in which one model execution could take several hours) can be enormous. Nevertheless, this paper describes an approach of using SA in such cases. The recommendations are obvious: simplifying the model as much as possible; considering just a key part of the model; and take more care about the speed of convergence. On this basis a case study on "Optimization of gas infrared heater radiation geometry" has been performed. The most interesting result is that the shape of the heater and the reflector material do not significantly influence the heat delivery to the occupied zone. The main conclusion is that Monte Carlo sensitivity analysis is not suitable for large CFD models with low level of abstraction. In order to obtain good results, we recommend to select a smaller part of the overall domain and/or to significantly simplify it

Sexuality and Health: A Study of Tanzanian Men\'s Experiences of Living with HIV/AIDS

The aim of this study was to explore Tanzanian men\'s experiences regarding their health and sex life after they had been diagnosed with HIV. In-depth interviews were performed with a purposive sample of ten men living in an urban area in Tanzania and who had been HIV positive for more than one year. A phenomenological-hermeneutic approach was used for analyzing the transcribed interviews. Three themes emerged from the texts; “awareness of HIV infection”, “perceived and ideal health”, and “sex life a source of happiness and caring”. Living with HIV meant profound adjustments to daily life activities for the participants. HIV forced them to learn new ways of having sexual intercourse and new ways of acting as a man. The meaning of being a “real man” had changed from being a man with great sexual prowess to being a “caring man” within one elationship.Keywords: HIV; sex life; phenomenological-hermeneutic method; interviewsAfrican Journal of Reproductive Health Vol. 12 (1) 2008: pp. 35-4

Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis

CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell–dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)/CD40 chimeric protein, promoted an increase in the number of follicular and marginal zone B cells in secondary lymphoid organs in transgenic mice. The B cells displayed an activated phenotype, prolonged survival and increased proliferation, but were significantly impaired in T cell-dependent immune responses. Constitutive CD40 signaling in B cells induced selective and constitutive activation of the noncanonical NF-κB pathway and the mitogen-activated protein kinases Jnk and extracellular signal–regulated kinase. LMP1/CD40-expressing mice older than 12 mo developed B cell lymphomas of mono- or oligoclonal origin at high incidence, thus showing that the interplay of the signaling pathways induced by constitutive CD40 signaling is sufficient to initiate a tumorigenic process, ultimately leading to the development of B cell lymphomas

Gastrointestinal decontamination in the acutely poisoned patient

ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data sourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study selection and data extractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data synthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient

Citlivostní analýza jako nástroj pro verifikaci CFD modelu a optimalizaci konkrétního prvku

Clánek zduraznuje význam volby vhodných okrajových podmínek pro správnost energetických simulacních výpoctu. Okrajové podmínky musí být vázány na úcel, pro který se simulacní výpocty provádí. Je predložen teoretický rozbor, metodologie a výsledky výpoctu ruzných okrajových podmínek stanovených z tepelných zisku pocítacu a monitoru využívaných pro administrativní práci. Jsou identifikovány klícové parametry pro volbu typu okrajových podmínek - pocet zarízení, která se na vnitrních tepelných ziscích podílí, a obecne známý rozdíl mezi statistickým a extrémním prubehem tepelných zisku (pro pocítace velmi výrazný). Prezentovaná metodologie výpoctu ruzných typu okrajových podmínek se opírá o teorii chyb a statistickou analýzu. Tyto nástroje jsou duležité pro stanovení relevantních okrajových podmínek

Accuracy in evaluation of view factors between small and far surfaces

The contribution describes an approach that can be used during evaluation of a view factor between complex emitter and planar absorber surfaces. Rather than sophisticated mathematical attitude, practical way is offered. The source surface is divided into smaller parts with same surface normal and using some minor assumptions, summary view factor is calculated. The contribution is aimed on an error that can be caused considering these assumptions and further on, on a case study (evaluation of a view factor between ceramic plaques source surface and a photometric sensor), real differences are shown