A cytosolic disulfide bridge‐supported dimerization is crucial for stability and cellular distribution of Coxsackievirus B3 protein 3A

RNA viruses in the Picornaviridae family express a large 250 kDa viral polyprotein that is processed by virus-encoded proteinases into mature functional proteins with specific functions for virus replication. One of these proteins is the highly conserved enteroviral transmembrane protein 3A that assists in reorganizing cellular membranes associated with the Golgi apparatus. Here, we studied the molecular properties of the Coxsackievirus B3 (CVB3) protein 3A with regard to its dimerization and its functional stability. By applying mutational analysis and biochemical characterization, we demonstrate that protein 3A forms DTT-sensitive disulfide-linked dimers via a conserved cytosolic cysteine residue at position 38 (Cys38). Homodimerization of CVB3 protein 3A via Cys38 leads to profound stabilization of the protein, whereas a C38A mutation promotes a rapid proteasome-dependent elimination of its monomeric form. The lysosomotropic agent chloroquine (CQ) exerted only minor stabilizing effects on the 3A monomer but resulted in enrichment of the homodimer. Our experimental data demonstrate that disulfide linkages via a highly conserved Cys-residue in enteroviral protein 3A have an important role in the dimerization of this viral protein, thereby preserving its stability and functional integrity

High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity.

Mammalian models of human disease are expensive and subject to ethical restrictions. Here, we present an independent platform for high-throughput screening, using larvae of the tobacco hornworm Manduca sexta, combining diagnostic imaging modalities for a comprehensive characterization of aberrant phenotypes. For validation, we use bacterial/chemical-induced gut inflammation to generate a colitis-like phenotype and identify significant alterations in morphology, tissue properties, and intermediary metabolism, which aggravate with disease progression and can be rescued by antimicrobial treatment. In independent experiments, activation of the highly conserved NADPH oxidase DUOX, a key mediator of gut inflammation, leads to similar, dose-dependent alterations, which can be attenuated by pharmacological interventions. Furthermore, the developed platform could differentiate pathogens from mutualistic gastrointestinal bacteria broadening the scope of applications also to microbiomics and host-pathogen interactions. Overall, larvae-based screening can complement mammals in preclinical studies to explore innate immunity and host-pathogen interactions, thus representing a substantial contribution to improve mammalian welfare

Spinal Deformity, Surgery at the Cervicothoracic Junction, and American Society of Anesthesiologists Class Increase the Risk of Post-surgical Intensive Care Unit Treatment after Dorsal Spine Surgery: A Single-Center Multivariate Analysis of 962 Patients

Study Design This was a retrospective multivariate analysis of preoperative risk factors leading to intensive care unit (ICU) admissions in patients undergoing elective or acute dorsal spine surgery. Purpose Numerous studies have predicted a substantial increase in spine surgeries within the next decades, potentially overwhelming hospitals’ resources, including ICU occupancy. Accurate estimates of whether patients need postsurgical ICU treatment are pivotal for both resource allocation and patient safety. Overview of Literature Risk factors leading to ICU admissions after dorsal spine surgery have been extensively examined for lumbar elective surgery. Studies including other anatomical segments of the spine and nonelective surgery regarding postsurgical ICU treatment probability are lacking. Methods This study was designed to be a single-center multivariate analysis of data retrospectively collected from a tertiary care university hospital. Patients undergoing dorsal spine surgery from 2009 to 2019 were included in this study. The patients’ demographic data were analyzed to determine potential preoperative risk factors for ICU admission after surgery using multiple logistic regression. Results In our cohort, 962 patients with a mean age of 71.1±0.55 years were included. Surgeries involved 3.24±0.08 spinal levels on average. The incidence of ICU treatment after surgery was 30.4% (n=292). Multivariate logistic regression showed a markedly increased odds ratio (OR) for patients undergoing surgery of the cervicothoracic junction (OR, 8.86) and those undergoing surgery for spinal deformity treatment (OR, 7.7). Additionally, cervical procedures (OR, 3.29), American Society of Anesthesiologists (ASA) class 3–4 (OR, 2.74), spondylodiscitis (OR, 2.47), fusion of ≥3 levels (OR, 1.94), and age >75 years (OR, 1.33) were associated with an increased risk of postsurgical ICU admission. Conclusions The findings highlight the relevance of anatomical location, preoperative diagnosis, ASA class, and length of surgery regarding the predictability of postoperative ICU admission. Our data allowed for more sophisticated estimates regarding the need for ICU treatment after dorsal spine surgery, guiding the surgeon through patient selection, communication, and ICU admission predictability

Postoperative management of weight bearing and rehabilitation after lumbar spinal surgery

Background Because of the growing trend of lumbar spinal surgery, it is essential for physicians and physiotherapists to develop standardized postoperative treatment. However, currently postoperative treatment after lumbar spinal surgery is controversial. Purpose of the study The purpose of this review article is to make recommendations for the postoperative treatment of lumbar intervertebral disc surgery, lumbar decompression surgery and lumbar spinal fusion surgery regarding mobilization, weight bearing and rehabilitation. These recommendations are based on current evidence and experience in our institution. Materials and methods A selective literature research of relevant publications was conducted in Pubmed. The studies are presented in tabular form. Results Patient training, accurate information about the postoperative course, information about limitations and stress possibilities as well as pain management seem to have an important role in the final outcome of the operation. Ideally, these procedures should be performed preoperatively or at the latest or repeatedly from the first postoperative day after lumbar spine surgery. Physiotherapy can have a positive impact on the clinical and functional outcome after lumbar disc, decompression and fusion surgery. Discussion Due to the heterogeneity of the intensity, duration and form of physiotherapy or rehabilitation, which are listed as interventions in the various studies, it is only possible to draw limited conclusions about general instructions for action on physiotherapy after spinal surgery

Is the use of modern versus conventional wound dressings warranted after primary knee and hip arthroplasty? Results of a Prospective Comparative Study

Purpose Of the Study:This prospective, open, non-controlled clinical investigation evaluated the performance of a modern post-operative wound dressing versus conventional dressings used on wounds of patients after undergoing hip or knee replacement. Methods:The clinical investigation started with a two-week observation phase of conventional wound dressings, followed by an intervention phase where patients were treated with Mepilex® Border Post-Op dressings. The primary objective was to evaluate the occurrence of blisters;Results:There was no blistering in any of the patients in the Mepilex group (n=49), whereas blistering occurred in 27.3% (n=3) of patients in the conventional group (n= 11, p<0.01). The Mepilex dressing was left on for seven days in 70% of patients. There was a significant reduction in the total cost for dressing changes with the Mepilex dressings (p=0.006). ConclusionBy using Mepilex dressings, the risk of blistering was negated and the reduced frequency of dressing changes was associated with the reduced overall cost. Therefore, we recommend the use of Mepilex Border Post-Op dressings

Terror und Anti-Terror. Politische Gewalt, Sicherheitspolitik und die strategische Kultur der Terrorismusbekämpfung in Deutschland

Vor dem Hintergrund des umfassenden sicherheitspolitischen Paradigmenwechsels der jüngeren Vergangenheit verfolgt die hier vorgelegte Arbeit ein zweifaches Interesse. Zunächst soll ein diffuser Untersuchungsgegenstand – Terrorismus als Form politischer Gewalt sowie die Methoden und Strategien seiner Bekämpfung – umfassend aufgehellt werden. Dabei wird nach der ratio terroristischen Handelns ebenso zu fragen sein, wie nach einer funktionalen Abgrenzung von ähnlichen, nicht aber gleichen Strategien politischer Veränderung. Es gibt keinen Terrorismus per se, weshalb kein terroristischer Archetyp beschrieben werden kann. Zur Unterscheidung terroristischer Akteure und Agenden ist infolgedessen eine Differenzierung nach sekundären Motiven und primären Zielsetzungen erforderlich. Die Literatur hat indessen eine Vielzahl unbrauchbarer Kategorisierungsversuche hervorgebracht, die entweder an Übersimplifizierung oder aber an übermäßig scholastischem Detailreichtum leiden. Auch hat sie bisweilen falsche, d. h. empirisch widerlegbare Schlüsse gezogen; etwa jener, wonach es sich bei Terrorismus um eine grundsätzlich erfolgversprechende Strategie handele. Aus der Unschärfe des Terrorismusbegriffs folgt die Unschärfe des Bekämpfungsdiskurses. Hier sollen entlang zweier grundsätzlicher Modellierungen der Auseinandersetzung („Terrorismus als Rechtsverletzung“ und „Terrorismus als Krieg“) die wesentlichen politischen, strategischen und taktischen Bezugspunkte einer allgemeinen Terrorismusbekämpfungskonzeption aufgezeigt werden. Insbesondere mit Blick auf den zweiten Teil der Arbeit wird in diesem Zusammenhang das gegenwärtige System der Terrorismusbekämpfung in Deutschland nach seinen Regeln und Akteuren differenziert. Dabei gilt es besonders, ihre materiellen Inhalte in die Systematik staatlicher Sicherheitsgewähr zu verorten. Dies erscheint zunächst schwierig, da eine Einordnung in die hergebrachte Dualität von äußerer oder innerer Sicherheit aufgrund einer funktionalen Entdifferenzierung in der staatlichen Sicherheitsproduktion kaum noch sinnvoll gelingt. Daneben stellt die Arbeit die Frage nach der Validität der bislang soweit ersichtlich nicht (oder nur unzureichend) empirisch und theoretisch fundierten These einer „realpolitischen Verschiebung“ in der deutschen Terrorismusbekämpfungspolitik seit dem 11. September 2001. Zur Beantwortung der Frage, ob sich Veränderungen in den normativen Grundlagen deutscher Antiterrorpolitik seit dem 11. 09. 2001 in Richtung eines realpolitischen Paradigmas nachweisen lassen, wird in dieser Arbeit das Instrument der strategischen Kulturanalyse herangezogen. Es geht davon aus, dass verschiedene Akteure aufgrund unterschiedlicher Vorstellungen von Sicherheit in vergleichbar erscheinenden strategischen Kontexten unterschiedliche Strategien verfolgen können

Is the use of modern versus conventional wound dressings warranted after primary knee and hip arthroplasty ? Results of a Prospective Comparative Study

Purpose of the Study : This prospective, open, non controlled clinical investigation evaluated the performance of a modern post-operative wound dressing versus conventional dressings used on wounds of patients after undergoing hip or knee replacement. Methods : The clinical investigation started with a two-week observation phase of conventional wound dressings, followed by an intervention phase where patients were treated with Mepilex (R) Border Post-Op dressings. The primary objective was to evaluate the occurrence of blisters. Results : There was no blistering in any of the patients in the Mepilex group (n = 49), whereas blistering occurred in 27.3% (n = 3) of patients in the conventional group (n = 11, p < 0.01). The Mepilex dressing was left on for seven days in 70% of patients. There was a significant reduction in the total cost for dressing changes with the Mepilex dressings (p = 0.006). Conclusion : By using Mepilex dressings, the risk of blistering was negated and the reduced frequency of dressing changes was associated with the reduced overall cost. Therefore, we recommend the use of Mepilex Border Post-Op dressings

The microvascular anatomy of the talus: a plastination study on the influence of total ankle replacement

The purpose of our study was to systematize the arterial supply of the talus and characterize the vessel damage occurring in the talus after total ankle replacement. Previous studies exist using vascular injection to visualize the topic [Giebel et al. (Surg Radiol Anat 19:231-235, 1997); Mulfinger and Trueta (J Bone Joint Surg Br 52:160-167, 1970); Peterson et al. (Acta Orthop Scand 46:1026-1034, 1975); Peterson and Goldie (Acta Orthop Scand 45:260-270, 1974)]. The vascularization of the talus has previously been described by various authors [Aquino et al. (J Foot Surg 25:188-193, 1986); Haliburton et al. (J Bone Joint Surg Am 40:1115-1120, 1958); Mulfinger and Trueta (1970); Peterson et al. (1975); Wildenauer (Z Orthop Ihre Grenzgeb 113:730, 1975)]. The plastination method provides excellent intraosseous view of the arterial system and offers a helpful method to demonstrate the influence of the Scandinavian Total Ankle Replacement (STAR) on the blood vessels. In a first step, the nutritive foramina were analyzed on 20 macerated cadaver feet. After this, the articular surface was measured with a print using Optosil. The next step was the visualization of the vascularization of the talus using the plastination method. After vascular injection, a STAR was implanted in two specimens and a plastination was done. The highest amount and density of nutritive foramina were found in the sulcus tali. Using the imprint technique for the examined tali, we found a mean area covered by cartilage of 56.9 % in comparison to the total surface. The deep fin of STAR has the potential to eliminate important blood vessels of the talus. The plastination methods were useful methods to analyze the arterial supply of the talus. In our study, the STAR showed a dominant influence on the vascularization of the talus. The fin appeared to be too long. A design modification with a short fin could provide the arterial supply, but should be tested biomechanically