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.     

Heat exchanger network synthesis with detailed exchanger designs: Part 1. A discretized differential algebraic equation model for shell and tube heat exchanger design

A new method for the detailed design of shell and tube heat exchangers is presented through the formulation of coupled differential heat equations, along with algebraic equations for design variables. Heat exchanger design components (tube passes, baffles, and shells) are used to discretize the differential equations and are solved simultaneously with the algebraic design equations. The coupled differential algebraic equation (DAE) system is suitable for numerical optimization as it replaces the nonsmooth log mean temperature difference (LMTD) term. Discrete decisions regarding the number of shells, fluid allocation, tube sizes, and number of baffles are determined by solving an LMTD-based method iteratively. The resulting heat exchanger topology is then used to discretize the detailed DAE model, which is solved as a nonlinear programming model to obtain the detailed exchanger design by minimizing an economic objective function through varying the tube length. The DAE model also provides the stream temperature profiles inside the exchanger simultaneously with the detailed design. It is observed that the DAE model results are almost equal to the LMTD-based design model for one-shell heat exchangers with constant stream properties but shows significant differences when streams properties are allowed to vary with temperature or the number of shells are increased. The accuracy of the solutions and the required computational costs show that the model is well suited for solving heat exchanger network synthesis problems combined with detailed exchanger designs, which is demonstrated in Part 2 of the paper.     

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.

     

Stability of a class of discrete-time nonlinear recursive observers

This work provides a framework for nominal and robust stability analysis for a class of discrete-time nonlinear recursive observers (DNRO). Given that the system has linear output mapping, local observability and Jacobian matrices satisfying certain conditions, the nominal and robust stability of the DNRO is defined by the property of estimation error dynamics and is analyzed using Lyapunov theory. Moreover, a simultaneous state and parameter estimation scheme is shown to be Input-to-State Stable (ISS), and adaptively reduce plant-model mismatch on-line. Three design strategies of the DNRO that satisfy the stability results are given as examples, including the widely used extended Kalman filter, extended Luenberger observer, and the fixed gain observer.