The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections

Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.     

Expression and Roles of Individual HIF Prolyl 4-Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium

The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1, 2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in Hif-p4h-1^−/−, Hif-p4h-2 hypomorph and Hif-p4h-3^−/− mice. Only Hif-p4h-2 hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs.     

Ärztliche Verantwortung gegenüber Palliativpatienten unter dem neuen Paradigma der Kundenorientierung

Definition of the problem

Establishing a good physician–patient relationship based on mutual trust and professional responsibility is a central element in physicians’ professionalism. Recently, however, there has been considerable debate in the field of medical ethics regarding trends toward an economic approach to medicine, which could potentially undermine healthy doctor–patient relationships. Part of this economic approach to medicine involves viewing the patient as an autonomous customer. But what does the customer role mean for vulnerable patients who are restricted in their autonomy and what effect does it have on the physician–patient relationship?

Arguments

In the following article, we pursue the question whether the physicians’ responsibility and the physician–patient relationship change when the (vulnerable) patient attributes the customer role to him-/herself. The study was conducted within the field of palliative care because terminally ill patients represent an especially vulnerable patient population. We base our argumentation in this article on the results of a qualitative interview study that investigated terminally ill patients’ attitudes regarding the topic “the patient as customer” as well as autonomy and decision-making.

Conclusion

The interview results show that autonomy must be understood in relational terms; furthermore, the analysis of the interviews indicates that the physician plays a crucial role in enabling the patient’s autonomy, regardless of whether patients view themselves as a patient or a customer. Subsequently, we deliberate whether the patients’ statements point to potential changes in the doctor–patient relationship and physicians’ responsibility towards patients. Based on these findings, practical implications for the doctor–patient relationship are considered in regard to the “Ethics of Care”, emphasizing the need for an individualized approach to working with patients, especially those with particularly vulnerable conditions.     

Paper‐Derived Ferroelectric Ceramics: A Feasibility Study

Preceramic paper may serve as a preform to manufacture single sheet as well as multilayer porous ferroelectric ceramic products. In this article, the authors discuss the formation, microstructure, and properties of preceramic papers highly loaded with BaTiO₃ filler ranging from 70 to 80 vol% and their conversion into ceramic materials. In order to increase the density of the single sheets, post calendering is applied. These sheets are used for the fabrication of multilayer ceramics using warm lamination technique. After binder burnout and sintering up to 1300 °C for 2 h in air, porous paper‐derived multilayer BaTiO₃ is obtained. The effect of ceramic filler content and calendering on the residual porosity in sintered samples is studied. Furthermore, the influence of porosity on the microstructure, mechanical, dielectric, and piezoelectric properties of the sintered BaTiO₃ ceramics is investigated.

     

命名数据网络中面向移动用户的内容预取方法*

针对命名数据网络(Named Data Networking, NDN)移动性增强支持不足的问题,基于城区移动场景提出了一种基于移动预测的内容预取方法(Mobility-aware Prediction Approach for Content Prefetching, MAP-CP)及扩展方案(extended MAP-CP, eMAP-CP)。MAP-CP和eMAP-CP通过预测移动用户的下一接入点(Access Point, AP),预取在当前AP下因切换AP不能获取到的Data并缓存到所预测的下一AP相关联的NDN节点中,为切换AP后的移动用户就近服务,达到降低内容获取延迟和提高响应率的目的。eMAP-CP在MAP-CP的基础上,可预取切换AP过程中请求的Data,能够进一步提高性能。基于ndnSIM的仿真实验表明,和NDN本身相比,MAP-CP和eMAP-CP具有更低的平均内容获取延迟和更高的响应率,而且eMAP-CP更优。在移动速度为20m/s,发包速率为200pps时,MAP-CP和eMAP-CP的平均内容获取延迟可分别降低约4.0%和38.7%,响应率可分别提高约1.2%和4.9%。     

Effect of Methionine Sulfoxide on the Synthesis and Purification of Aggregation-Prone Peptides

A two-step synthesis for methionine-containing hydrophobic and/or aggregation-prone peptides is presented that takes advantage of the reversibility of methionine oxidation. The use of polar methionine sulfoxide as a building block in solid-phase peptide synthesis improves the synthesis quality and yields the crude peptide, with significantly improved solubility compared to the reduced species. This facilitates the otherwise often laborious peptide purification by high-performance liquid chromatography. The subsequent reduction proceeds quantitatively. This approach has been optimised with the methionine-rich Tar-DNA-binding protein 43 (307–347), but is also more generally applicable, as demonstrated by the syntheses of human calcitonin and two aggregation-prone peptides from the human prion protein.