Herderlijke regel of inburgeringscursus? Een bijdrage aan het onderzoek naar de ethische richtlijnen in 1 Timoteüs & Titus

Within the debate about Paul’s authorship, Klinker concentrates on one specific point of debate: the question whether the Pastoral Epistles are intended as “pastoral instruction” of Paul to his collaborators Timothy and Titus, or as documents arising at a later time that promote a kind of “assimilated” lifestyle for Christians. “Because of the delay of Christ’s return, the need arose for a more permanent place for Christians in society—that is the currently reigning opinion. The Pastoral Epistles are then a collection of advice to believers so that they, among other things, assimilate respectably into the social conventions prevailing in that time—a kind of ‘lesson about integration.’ Until the nineteenth century people assumed that the Pastoral Epistles were a ‘pastoral rule’ and it was general accepted that Paul was the author. Subsequently the notion of the ‘lesson about integration’ gained ground and it was accepted that later Christians had Paul’s name affixed to their letters in order to lend authority to those documents.” In contemporary discussions, the “ancient” view hardly counts any longer. Nevertheless, according to Klinker, precisely this view contains much that helps explain the differences between the “conventional” advice in the Pastoral Epistles, and the advice we find in the undisputed letters of Paul. She attempts to demonstrate this by comparing the prescriptions about the man-woman relationship in 1 Timothy and Titus with those in 1 Corinthians

Use of simulation training to teach the ABCDE primary assessment:an observational study in a Dutch University Hospital with a 3-4 months follow-up

Objectives To investigate short-term and long-term effectiveness of simulation training to acquire a structured Airway Breathing Circulation Disability Exposure (ABCDE) approach for medical emergencies; and to examine which skills were learnt and maintained best. Design An observational study with a 3-4 months follow-up. Setting Skills center of the University Medical Center Groningen. Participants Thirty voluntary participants (21 females and 9 males; 27±2.77 years) of a simulation-based course. Intervention A 2-day ABCDE-teaching course for residents and non-residents. The course encompasses 24 simulations in which participants perform primary assessments of acute ill patients. Video recordings were taken of each participant performing a primary assessment, before (T1), directly after (T2) and 3-4 months after the intervention (T3). Main outcome measures Physicians' performance in the ABCDE primary assessment at T1, T2 and T3. Two observers scored the primary assessments, blinded to measurement moment, using an assessment form to evaluate the performance with regard to skills essential for a structured ABCDE approach. The Friedman and Wilcoxon signed-rank test were used to compare physicians' performances on the subsequent measurement moments. Results The mean ranks on the total primary assessment at T1, T2 and T3 were 1.14, 2.62 and 2.24, respectively, and were significantly different, (p<0.001). The mean ranks on the total primary assessment directly after the course (T2 vs T1 p<0.001) and 3-4 months after the course (T3 vs T1 p<0.001) were significantly better than before the course. Certain skills deteriorated during the follow-up. Strikingly, most skills that decrease over time are Crew Resources Management (CRM) skills. Conclusion A course using simulation training is an effective educational tool to teach physicians the ABCDE primary assessment. Certain CRM skills decrease over time, so we recommend organising refresher courses, simulation team training or another kind of simulation training with a focus on CRM skills

Defective CD4(+)CD25(+ )regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-γ

Mice with a deficiency in IFN-γ or IFN-γ receptor (IFN-γR) are more susceptible to collagen-induced arthritis (CIA), an experimental autoimmune disease that relies on the use of complete Freund's adjuvant (CFA). Here we report that the heightened susceptibility of IFN-γR knock-out (KO) mice is associated with a functional impairment of CD4(+)CD25(+ )T(reg )cells. Treatment of wild-type mice with depleting anti-CD25 antibody after CFA-assisted immunisation with collagen type II (CII) significantly accelerated the onset of arthritis and increased the severity of CIA. This is an indication of a role of T(reg )cells in the effector phase of CIA. IFN-γR deficiency did not affect the number of CD4(+)CD25(+ )T cells in the central and peripheral lymphoid tissues. In addition, CD4(+)CD25(+ )T cells isolated from naive IFN-γR KO mice had a normal potential to suppress T cell proliferation in vitro. However, after immunisation with CII in CFA, the suppressive activity of CD4(+)CD25(+ )T cells became significantly more impaired in IFN-γR-deficient mice. Moreover, expression of the mRNA for Foxp3, a highly specific marker for T(reg )cells, was lower. We further demonstrated that the effect of endogenous IFN-γ, which accounts for more suppressive activity in wild-type mice, concerns both T(reg )cells and accessory cells. Our results demonstrate that the decrease in T(reg )cell activity in CIA is counter-regulated by endogenous IFN-γ

Technical feasibility of online adaptive stereotactic treatments in the abdomen on a robotic radiosurgery system

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) has been proven to be beneficial for several disease sites in the (lower) abdomen. However, the quality of the treatment plan, based on a single planning computed tomography (CT), can be compromised due to large inter-fraction motion of the target and organs at risk (OARs) in this anatomical region. The aim of this study was to investigate the feasibility of online adaptive SBRT treatments on a robotic radiosurgery system and to record estimated total treatment times. MATERIALS AND METHODS: For two disease sites, locally advanced pancreatic cancer (LAPC) and oligometastatic lymph nodes, four patients with repeat CTs were included in the feasibility study. Quick treatment plan templates were generated based on the planning CT and validated by running them on the plan and fraction CTs. For two cases a dummy run was performed and the individual steps were timed. Dose delivery was the largest contributor to the total treatment time, followed by contour adaptation. RESULTS: Running the quick plan templates resulted in plans similar to unrestricted plans, obeying the OAR constraints. The dummy runs showed that online adaptive treatments were completed in 64 to 83 min respectively for oligometastases and LAPC, comparable to other clinically available solutions. CONCLUSIONS: This study showed the feasibility of online re-planning for two challenging disease sites within a clinically acceptable time frame on a robotic radiosurgery system, making use of commercially available elements that are not integrated by the vendor

A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients:Should We Aim for Less?

Introduction. Despite widespread and liberal use of oxygen supplementation, guidelines about rational use of oxygen are scarce. Recent data demonstrates that current protocols lead to hyperoxemia in the majority of the patients and most health care professionals are not aware of the negative effects of hyperoxemia. Method. To investigate the effects of hyperoxemia in acutely ill patients on clinically relevant outcomes, such as neurological and functional status as well as mortality, we performed a literature review using Medline (PubMed) and Embase. We used the following terms: hyperoxemia OR hyperoxemia OR [“oxygen inhalation therapy” AND (mortality OR death OR outcome OR survival)] OR [oxygen AND (mortality OR death OR outcome OR survival)]. Original studies about the clinical effects of hyperoxemia in adult patients suffering from acute or emergency illnesses were included. Results. 37 articles were included, of which 31 could be divided into four large groups: cardiac arrest, traumatic brain injury (TBI), stroke, and sepsis. Although a single study demonstrated a transient protective effect of hyperoxemia after TBI, other studies revealed higher mortality rates after cardiac arrest, stroke, and TBI treated with oxygen supplementation leading to hyperoxemia. Approximately half of the studies showed no association between hyperoxemia and clinically relevant outcomes. Conclusion. Liberal oxygen therapy leads to hyperoxemia in a majority of patients and hyperoxemia may negatively affect survival after acute illness. As a clinical consequence, aiming for normoxemia may limit negative effects of hyperoxemia in patients with acute illness

Enhanced osteoclast development in collagen-induced arthritis in interferon-γ receptor knock-out mice as related to increased splenic CD11b(+ )myelopoiesis

Collagen-induced arthritis (CIA) in mice is accompanied by splenomegaly due to the selective expansion of immature CD11b(+ )myeloblasts. Both disease manifestations are more pronounced in interferon-γ receptor knock-out (IFN-γR KO) mice. We have taken advantage of this difference to test the hypothesis that the expanding CD11b(+ )splenic cell population constitutes a source from which osteoclast precursors are recruited to the joint synovia. We found larger numbers of osteoclasts and more severe bone destruction in joints of IFN-γR KO mice than in joints of wild-type mice. Osteoclast-like multinucleated cells appeared in splenocyte cultures established in the presence of macrophage colony-stimulating factor (M-CSF) and stimulated with the osteoclast-differentiating factor receptor activator of NF-κB ligand (RANKL) or with tumour necrosis factor-α (TNF-α). Significantly larger numbers of such cells could be generated from splenocytes of IFN-γR KO mice than from those of wild-type mice. This was not accompanied, as might have been expected, by increased concentrations of the intracellular adaptor protein TRAF6, known to be involved in signalling of RANKL- and TNF-α-induced osteoclast formation. Splenocyte cultures of IFN-γR KO mice also produced more TNF-α and more RANKL than those of wild-type mice. Finally, splenocytes isolated from immunised IFN-γR KO mice contained comparatively low levels of pro-interleukin-1β (pro-IL-1β) and pro-caspase-1, indicating more extensive conversion of pro-IL-1β into secreted active IL-1β. These observations provide evidence that all conditions are fulfilled for the expanding CD11b(+ )splenocytes to act as a source of osteoclasts and to be indirectly responsible for bone destruction in CIA. They also provide a plausible explanation for the higher susceptibility of IFN-γR KO mice to CIA

Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis

CXCL12 (stromal cell-derived factor 1) is a unique biological ligand for the chemokine receptor CXCR4. We previously reported that treatment with a specific CXCR4 antagonist, AMD3100, exerts a beneficial effect on the development of collagen-induced arthritis (CIA) in the highly susceptible IFN-γ receptor-deficient (IFN-γR KO) mouse. We concluded that CXCL12 plays a central role in the pathogenesis of CIA in IFN-γR KO mice by promoting delayed type hypersensitivity against the auto-antigen and by interfering with chemotaxis of CXCR4(+ )cells to the inflamed joints. Here, we investigated whether AMD3100 can likewise inhibit CIA in wild-type mice and analysed the underlying mechanism. Parenteral treatment with the drug at the time of onset of arthritis reduced disease incidence and modestly inhibited severity in affected mice. This beneficial effect was associated with reduced serum concentrations of IL-6. AMD3100 did not affect anti-collagen type II antibodies and, in contrast with its action in IFN-γR KO mice, did not inhibit the delayed type hypersensitivity response against collagen type II, suggesting that the beneficial effect cannot be explained by inhibition of humoral or cellular autoimmune responses. AMD3100 inhibited the in vitro chemotactic effect of CXCL12 on splenocytes, as well as in vivo leukocyte infiltration in CXCL12-containing subcutaneous air pouches. We also demonstrate that, in addition to its effect on cell infiltration, CXCL12 potentiates receptor activator of NF-κB ligand-induced osteoclast differentiation from splenocytes and increases the calcium phosphate-resorbing capacity of these osteoclasts, both processes being potently counteracted by AMD3100. Our observations indicate that CXCL12 acts as a pro-inflammatory factor in the pathogenesis of autoimmune arthritis by attracting inflammatory cells to joints and by stimulating the differentiation and activation of osteoclasts