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Die Visite ist ein wichtiges und in der Wertigkeit unterschatztes Instrument der spitalinternistischen Tatigkeit. Es fehlen dafur weitgehend Standards und klare Rahmenbedingungen. Eine strukturierte Visite ist fur alle beteiligten Berufsgruppen und vor allem fur die Patientinnen und Patienten gewinnbringend.

BackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

Influenza remains a global health risk and challenge. Currently, neuraminidase (NA) inhibitors are extensively used to treat influenza, but their efficacy is compromised by the emergence of drug-resistant variants. Neutralizing antibodies targeting influenza A virus surface glycoproteins are critical components of influenza therapeutic agents and may provide alternative strategies to the existing countermeasures. However, the major hurdle for the extensive application of antibody therapies lies in the difficulty of generating nonimmunogenic antibodies in large quantities rapidly. Here, we report that one human monoclonal antibody (MAb), 53C10, isolated from transchromosomic (Tc) cattle exhibits potent neutralization and hemagglutination inhibition titers against different clades of H1N1 subtype influenza A viruses. In vitro selection of antibody escape mutants revealed that 53C10 recognizes a novel noncontinuous epitope in the hemagglutinin (HA) head domain involving three amino acid residues, glycine (G), serine (S), and glutamic acid (E) at positions 172, 207, and 212, respectively. The results of our experiments supported a critical role for substitution of arginine at position 207 (S207R) in mediating resistance to 53C10, while substitutions at either G172E or E212A did not alter antibody recognition and neutralization. The E212A mutation may provide structural stability for the epitope, while the substitution G172E probably compensates for loss of fitness introduced by S207R. Our results offer novel insights into the mechanism of action of MAb 53C10 and indicate its potential role in therapeutic treatment of H1 influenza virus infection in humans. IMPORTANCE Respiratory diseases caused by influenza viruses still pose a serious concern to global health, and neutralizing antibodies constitute a promising area of antiviral therapeutics. However, the potential application of antibodies is often hampered by the challenge in generating nonimmunogenic antibodies in large scale. In the present study, transchromosomic (Tc) cattle were used for the generation of nonimmunogenic monoclonal antibodies (MAbs), and characterization of such MAbs revealed one monoclonal antibody, 53C10, exhibiting a potent neutralization activity against H1N1 influenza viruses. Further characterization of the neutralization escape mutant generated using this MAb showed that three amino acid substitutions in the HA head domain contributed to the resistance. These findings emphasize the importance of Tc cattle in the production of nonimmunogenic MAbs and highlight the potential of MAb 53C10 in the therapeutic application against H1 influenza virus infection in humans.

Summary Iron (Fe) and zinc (Zn) deficiencies are a global human health problem that may worsen by the growth of crops at elevated atmospheric CO 2 concentration (eCO 2). However, climate change will also involve higher temperature, but it is unclear how the combined effect of eCO 2 and higher temperature will affect the nutritional quality of food crops. To begin to address this question, we grew soybean (Glycine max) in a Temperature by Free‐Air CO 2 Enrichment (T‐FACE) experiment in 2014 and 2015 under ambient (400 μmol mol−1) and elevated (600 μmol mol−1) CO 2 concentrations, and under ambient and elevated temperatures (+2.7°C day and +3.4°C at night). In our study, eCO 2 significantly decreased Fe concentration in soybean seeds in both seasons (−8.7 and −7.7%) and Zn concentration in one season (−8.9%), while higher temperature (at ambient CO 2 concentration) had the opposite effect. The combination of eCO 2 with elevated temperature generally restored seed Fe and Zn concentrations to levels obtained under ambient CO 2 and temperature conditions, suggesting that the potential threat to human nutrition by increasing CO 2 concentration may not be realized. In general, seed Fe concentration was negatively correlated with yield, suggesting inherent limitations to increasing seed Fe. In addition, we confirm our previous report that the concentration of seed storage products and several minerals varies with node position at which the seeds developed. Overall, these results demonstrate the complexity of predicting climate change effects on food and nutritional security when various environmental parameters change in an interactive manner., Significance statement Mineral deficiencies are a global health problem that may be exacerbated by crop growth at elevated atmospheric CO2 concentration (eCO2) that can reduce micronutrient concentrations in grains and seeds. However, our soybean studies suggest that the potential threat to human nutrition by increasing CO2 concentration may not be realized when plants grow at eCO2 and higher temperatures that more realistically mimic future climate conditions.

A 33-year old Romanian chef presented with sudden onset of chest pain and chills as well as a significant elevation of myocardial markers and CRP.Coronary angiography showed no signs of relevant atherosclerosis. A myocarditis was assumed and later diagnosed on cardiac MRI.Due to fevers up to 40 °C and occupational history, Q fever was assumed. Serologic findings confirmed the diagnosis.After the start of antibiotic treatment, temperatures remained normal and the patient could be discharged a few days later. Azithromycin was recommended for several weeks to prevent a chronic infection. At the check-up visit one month later the patient appeared to have no signs of chronic heart failure or persistent infection.Myocarditis is a rare manifestation of Q fever, which should not be missed. The diagnostic evaluation with antibody titers is easy. The antibiotic therapy is well tolerated and is a causal treatment that helps to prevent long-term damage.Ein 33-jähriger Koch stellte sich notfallmäßig mit Angina pectoris und Schüttelfrost sowie signifikant erhöhten Troponin-, CK- und CRP-Werten vor.Eine koronare Herzerkrankung wurde koronarangiografisch ausgeschlossen. Der Verdacht auf eine akute Myokarditis erhärtete sich später MR-morphologisch.Aufgrund von Fieberschüben und Berufsanamnese vermuteten wir eine Q-Fieber-Erkrankung, die sich serologisch bestätigte.Unter antimikrobieller Therapie sistierte das Fieber und der Patient konnte wenige Tage später entlassen werden. Zur Vermeidung einer Chronifizierung empfahlen wir eine mehrwöchige Azithromycin-Therapie. Nach 1 Monat imponierte der Patient in einem guten klinischen Zustand ohne Zeichen einer Herzinsuffizienz oder Anhalt für eine persistierende Infektion.Myokarditis ist eine sehr seltene Erscheinungsform von Q-Fieber, die nicht übersehen werden sollte. Die Diagnostik mittels Antikörpertiter ist leicht durchführbar. Die antibiotische Therapie ist gut verträglich, behandelt die Myokarditis kausal und dient der Vermeidung von Langzeitschäden.

Syncope is defined as a transient, self-limited loss of consciousness due to insufficient cerebral blood perfusion. In a clinical setting, syncopal events usually present a diagnostic dilemma due to its broad differential diagnosis ranging from banal to potentially harmful causes. In the absence of a working hypothesis, multiple tests are ordered that result in high costs but are of questionable diagnostic and therapeutic value. This article provides a practical overview and, based on international guidelines and selected studies, proposes a standardized approach to patients with syncope. Initial evaluation of these patients includes taking a careful medical history, physical examination and ECG. These tests result in an individual risk assessment that supports decision-making whether further analysis should be performed in an outpatient or inpatient setting. Additional tests including echocardiography, laboratory analysis, cardiac monitoring, CT-scans, are ordered according to prior evaluation. This article reviews the most common diagnostic tests, their indications and the clinical relevance for the evaluation of patients with syncopal events. Therapeutic options are not within the focus of this article.

Purpose Clinical decision support (CDS) software designed around the ACR Appropriateness Criteria assists health care providers in choosing appropriate imaging studies at the time of order entry. The goal of this study was to determine the impact of commercially available CDS on the ordering habits of inpatient and emergency providers. Methods In 2014, ACR Select was integrated into our electronic health record, though without displaying appropriateness scores in a “silent” mode for 6 months. Then, feedback regarding examination appropriateness was “turned on” at order entry for adult patients in the emergency and inpatient settings for 24 months. We retrospectively compared the appropriateness scores of imaging tests before and after displaying feedback at order entry and evaluated these data by modality and attending versus trainee status. Results The commercially available CDS-generated scores for 34% and 20.4% of pre- and postintervention studies, respectively. After feedback, the relative frequency of low utility studies decreased to 5.4% from 11%, and the relative frequency of indicated studies increased to 82% from 64.5%. This was most pronounced in trainees for whom the percentage of low utility studies decreased from 10.8% (95% confidence interval [CI]: 10.0%, 11.7%) to 4.8% (95% CI: 4.4%, 5.2%) and the percentage of indicated studies increased from 65.6% (95% CI: 64.3%, 66.9%) to 83.7% (83.0%, 84.3%). Conclusions After implementation of a commercially available decision support tool integrated into the electronic health record, there was a significant improvement in imaging study appropriateness scores, more pronounced in studies ordered by trainees.

Some STR loci have internal sequence variations, which are not revealed by the standard STR typing methods used in forensic genetics (PCR and fragment length analysis by capillary electrophoresis (CE)). Typing of STRs with next-generation sequencing (NGS) uncovers the sequence variation in the repeat region and in the flanking regions. In this study, 363 Danish individuals were typed for 56 STRs (26 autosomal STRs, 24 Y-STRs, and 6 X-STRs) using the ForenSeq™ DNA Signature Prep Kit to establish a Danish STR sequence database. Increased allelic diversity was observed in 34 STRs by the PCR-NGS assay. The largest increases were found in DYS389II and D12S391, where the numbers of sequenced alleles were around four times larger than the numbers of alleles determined by repeat length alone. Thirteen SNPs and one InDel were identified in the flanking regions of 12 STRs. Furthermore, 36 single positions and five longer stretches in the STR flanking regions were found to have dubious genotyping quality. The combined match probability of the 26 autosomal STRs was 10,000 times larger using the PCR-NGS assay than by using PCR-CE. The typical paternity indices for trios and duos were 500 and 100 times larger, respectively, than those obtained with PCR-CE. The assay also amplified 94 SNPs selected for human identification. Eleven of these loci were not in Hardy-Weinberg equilibrium in the Danish population, most likely because the minimum threshold for allele calling (30 reads) in the ForenSeq™ Universal Analysis Software was too low and frequent allele dropouts were not detected.

Zusammenfassung. Ein kavernierender oder kavitierender Lungenrundherd bzw. eine Lungenkaverne ist die Manifestation einer grossen Bandbreite von pathologischen Prozessen mit Befall der Lunge inklusive entzündlicher, infektiöser und maligner Ätiologien. Gleichzeitig kann das Vorhandensein einer Kaverne im klinischen Kontext helfen, die Differenzialdiagnosen und damit die weiteren Abklärungsschritte einzugrenzen. Wir werden im Folgenden einen Überblick über mögliche Diagnosen und die entsprechenden klinischen und radiologischen Zeichen kavernierender Lungenrundherde darlegen; ein besonderer Fokus wird dabei auf Vaskulitiden gelegt.

Influenza virus infections remain a significant health burden worldwide, despite available vaccines. Factors that contribute to this include a lack of broad coverage by current vaccines and continual emergence of novel virus strains. Further complicating matters, when influenza viruses infect a host, severe infections can develop when bacterial pathogens invade. Secondary bacterial infections (SBIs) contribute to a significant proportion of influenza-related mortality, with Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae as major coinfecting pathogens. Vaccines against bacterial pathogens can reduce coinfection incidence and severity, but few vaccines are available and those that are, may have decreased efficacy in influenza virus-infected hosts. While some studies indicate a benefit of vaccine-induced immunity in providing protection against SBIs, a comprehensive understanding is lacking. In this review, we discuss the current knowledge of viral and bacterial vaccine availability, the generation of protective immunity from these vaccines, and the effectiveness in limiting influenza-associated bacterial infections.

Calcium (Ca2+) serves as a universal second messenger in eukaryotic signal transduction. Understanding the Ca2+ activation kinetics of Ca2+ sensors is critical to understanding the cellular signaling mechanisms involved. In this review, we discuss the regulatory properties of two sensor classes: the Ca2+-dependent protein kinases (CPKs/CDPKs) and the calcineurin B-like (CBL) proteins that control the activity of CBL-interacting protein kinases (CIPKs) and identify emerging topics and some foundational points that are not well established experimentally. Most plant CPKs are activated by physiologically relevant Ca2+ concentrations except for those with degenerate EF hands, and new results suggest that the Ca2+-dependence of kinase activation may be modulated by both protein–protein interactions and CPK autophosphorylation. Early results indicated that activation of plant CPKs by Ca2+ occurred by relief of autoinhibition. However, recent studies of protist CDPKs suggest that intramolecular interactions between CDPK domains contribute allosteric control to CDPK activation. Further studies are required to elucidate the mechanisms regulating plant CPKs. With CBL–CIPKs, the two major activation mechanisms are thought to be (i) binding of Ca2+-bound CBL to the CIPK and (ii) phosphorylation of residues in the CIPK activation loop. However, the relative importance of these two mechanisms in regulating CIPK activity is unclear. Furthermore, information detailing activation by physiologically relevant [Ca2+] is lacking, such that the paradigm of CBLs as Ca2+ sensors still requires critical, experimental validation. Developing models of CPK and CIPK regulation is essential to understand how these kinases mediate Ca2+ signaling and to the design of experiments to test function in vivo.

Zusammenfassung. Unter dem Begriff «Porphyrie» wird eine Gruppe von acht Stoffwechselerkrankungen zusammengefasst, welche in Folge einer gestörten Hämbiosynthese entstehen. Die Einteilung der verschiedenen Formen erfolgt anhand der klinischen und biochemischen Merkmale. Dieser Artikel fokussiert auf die akuten (hepatischen) Porphyrien (AHP), die durch eine ähnliche Pathophysiologie und klinische Symptomatik gekennzeichnet sind. Typisch sind akute, das autonome Nervensystem betreffende Symptome; starke, kolikartige, teilweise ausstrahlende Oberbauchschmerzen, Übelkeit, Erbrechen, Hypertonie, Tachykardie, Obstipation und Hyponatriämie. Die Diagnose einer AHP wird aufgrund einer mindestens fünffach erhöhten Ausscheidung von Porphobilinogen (PBG) im Urin gestellt. Therapie der Wahl ist die Zufuhr von Kohlenhydraten, die Gabe von humanem Häm, die Elimination und Vermeidung von schubauslösenden Triggerfaktoren und eine begleitende symptomorientierte Therapie, im Besonderen eine suffiziente Analgesie.

Novel nanocarbons synthesized by extreme conditions produce products with various chemical and physical properties. Herein through high explosive detonation of Composition B-3 (40% TNT, 60% RDX), pressures and temperatures not classically attainable in laboratory syntheses provide access to interesting carbon allotropes. For example, detonations of Composition B-3 are regularly used to synthesize the now commercially-available nanodiamond (3–5 nm spherical diamond particles) through quenching of the detonation by ice collars at high pressures and temperatures. Detonation conditions of Composition B-3, in this study, were modified by altering the atmosphere (air versus Ar) without quenching, consequently directing nanocarbon formation. X-ray scattering and microscopy elucidate that detonations performed in air produced spherical hollow core-shell nanocarbons, whereas detonations in Ar produced elongated nanocarbons. Although morphology bifurcates, spectroscopy reveals that both major detonation products are comprised of sp2 hybridized carbon. As expected from air atmosphere detonations, surface functionalization is dominated by C O bonding. The absence of oxygen in the Ar atmosphere detonations may propagate extended sheets of graphene that either stack together due to electrostatics or fold upon itself. This work demonstrates that modification of the detonation atmosphere provides an alternative route for the production of new and interesting nanocarbons.

Insbesondere bei Biegeträgern im Ingenieurholzbau mit Ausklinkungen und Öffnungen, geneigtem Obergurt und im Bereich von Queranschlüssen steht die Zugspannung quer zur Holzfaserrichtung als bemessungsrelevante Größe im Vordergrund. In diesen Fällen bestimmt die vergleichsweise geringe Querzugfestigkeit die Grenzen der Tragfähigkeit der Konstruktion. Für Holz liegen diesbezüglich verschiedene, zum Teil widersprüchliche Angaben auf Basis von sehr unterschiedlichen, in einem Großteil der Fälle einaxialen Bestimmungsmethoden vor. Als Ergänzung hierzu und mit Hinblick auf eine möglichst sichere Bemessung von querzugbeanspruchten Strukturen erfolgten versuchstechnische und rechnerische Untersuchungen auf Basis von 50 Kleinbiegeproben (Fichtenholz im Vierpunktbiegeversuch) mit unterschiedlichen Ausklinkungen in Feldmitte. Bestimmt wurden die äußere Lastaufnahmefähigkeit, das Durchbiegungsverhalten sowie das Dehnungs- und Rissverhalten im kritischen Eckbereich der Öffnungen. Mittels eines mehrdimensionalen Bruchkriteriums wurden anhand der gemessenen Bruchlasten die Querzugfestigkeiten rückgerechnet. Aufgrund der speziellen Probenform liefern die Messungen auch Aussagen über die globale Lastkapazität von ausgeklinkten Trägern in Kleinformat, wozu es in der Literatur auch ein entsprechendes Bemessungsverfahren gibt. Es zeigten sich, dass das dort beschriebene Bemessungsverfahren auf globalem Lastniveau die messtechnisch ermittelten Kapazitäten maßgebend unterschätzt.

Polymers are widely implemented materials often used for safety and security in our daily lives. However, we do not have a thorough understanding of the phase transformations of these materials when exposed to extreme condition, high strain rate events. To study polymers in these severe environments, we performed plate impact experiments that impart a one-dimensional shockwave, at high pressures and temperatures, to observe the materials response. Generally, velocimetry is the experimental diagnostic used to capture the movement of high velocity interfaces to then calculate the mechanical variables associated with shock compression. However, when a material undergoes a phase transition, such as between two crystalline phases or melting to decomposition during shock compression, velocimetry does not explicitly indicate what structural change occurred. At the Dynamic Compression Sector at the Advanced Photon Source, gas gun driven compression has been paired with x-ray diffraction, providing the ability to study both the shock parameters and structural changes concurrently. We explored high density polyethylene (HDPE) both on its reactants Hugoniot (

Growing evidence supports the importance of protein S-glutathionylation as a regulatory post-translational modification with functional consequences for proteins. Discoveries of redox-state-dependent protein kinase S-glutathionylation have fueled discussion of redox-sensitive signaling. Following previously published experimental evidence for S-glutathionylation induced deactivation of the Arabidopsis thaliana kinase BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1), we investigated the consequences of S-glutathionylation on the equilibrium conformational ensemble of BAK1 using all-atom molecular dynamics simulations. We found that glutathionylation of C408 allosterically destabilizes the active-like state of BAK1 and stabilizes an inactive conformation known to recur in protein kinases. Glutathionylation of C408 also has structural consequences throughout the BAK1 kinase domain, whereas glutathionylation of C353 in the N-lobe and C374 near the ATP-binding site have few notable effects on BAK1 compared with the unmodified protein. Our results suggest an allosteric mechanism for inhibition of BAK1 by C408 S-glutathionylation, and more generally, support the notion of protein kinase S-glutathionylation as a means of redox signaling in plant cells.

Pulmonary embolism (PE), specifically submassive and massive, can be life threatening. Pulmonary embolism response teams (PERTs) are being developed across the country to facilitate rapid diagnosis and appropriate triage and provide rapid personalized treatment to reduce early cardiopulmonary decompensation and mortality. Early results are promising and demonstrate improved patient outcomes. Providers treating patients with PE should be familiar with PERT methodology to improve the diagnosis and treatment of PE.

New generation devices for long-term mechanical circulatory support are centrifugal pumps having fully magnetically levitated rotors to reduce blood trauma. Recently, the novel HeartMate 3 was cleared for clinical application in Switzerland. In two Swiss University Hospitals part of the "Lausanne-Geneva Transplantation Network," 10 consecutive patients in end-stage heart failure received the HeartMate 3 (Thoratec Corporation, Pleasanton, CA). Device implantation criteria were persistent low output syndrome despite optimal medical treatment. The primary end-point of the study was survival or transplantation to 90 days on the device. Five patients (50%) were in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 1 and 2 (two were under venoarterial extracorporeal membrane oxygenation [VA-ECMO]), and five were in class 3 and 4. The indication was bridge-to-transplant in seven patients, and destination therapy in three. Two patients (20%) received concomitant aortic valve surgery. Four patients (40%) required temporary right ventricle support (tRVAD) for a mean of 8 ± 1.5 days. Bleeding requiring surgical revision occurred in five (50%) patients, two during the tRVAD support. At the 90 day end-point, survival was 90%, one (10%) died due to respiratory failure. Three (30%) experienced critical illness polyneuropathy. Two had body temperature over 38.5°C for more than 7 days after implant, without infections. Two (20%) had late driveline infection. The pump allowed rapid improvement of patients' clinical conditions even in severely compromised patients. Postoperative bleeding occurred in the setting of anticoagulation. No hemolysis or pump thrombosis occurred. Fever occurred frequently but was not associated with mortality. Hemodynamic support was consistent over time without significant adverse events.

Zusammenfassung. Das akute Koronarsyndrom bleibt weltweit eine führende Ursache für Morbidität und Mortalität. Deshalb sind die rasche Diagnosestellung und die Wahl des Therapieansatzes von entscheidender Bedeutung. Das optimale Timing für Intervention und Revaskularisation hängt von der initialen Risikostratifikation ab. Patienten mit hämodynamischer Instabilität oder kardiogenem Schock, lebensbedrohlichen Arrhythmien, refraktärer Angina pectoris oder schwerer Herzinsuffizienz sollten unabhängig von EKG-Veränderungen oder kardialen Biomarkern einer sofortigen Koronarangiografie zugeführt werden. Patienten mit NSTEMI oder instabiler Angina pectoris mit entsprechend hohem Risikoprofil profitieren von einer frühinvasiven Abklärung innerhalb von 24 h. Ein frühinvasiver Therapieansatz bei Patienten mit NSTEMI ist sicher und mit einer geringeren Anzahl refraktärer Ischämien und einem kürzeren Spitalaufenthalt assoziiert. Weniger klar ist die Situation bei asymptomatischen und stabilen Patienten mit NSTEMI, bei denen eine Latenz bis maximal 72 h vertretbar ist.

The detonation of carbon-rich high explosives yields solid carbon as a major constituent of the product mixture, and depending on the thermodynamic conditions behind the shock front, a variety of carbon allotropes and morphologies may form and evolve. We applied time-resolved small-angle X-ray scattering (TR-SAXS) to investigate the dynamics of carbon clustering during detonation of PBX 9502, an explosive composed of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and 5 wt % fluoropolymer binder. Solid carbon formation was probed from 0.1 to 2.0 μs behind the detonation front and revealed rapid carbon cluster growth which reached a maximum after ∼200 ns. The late-time carbon clusters had a radius of gyration of 3.3 nm which is consistent with 8.4 nm diameter spherical particles and matched particle sizes of recovered products. Simulations using a clustering kinetics model were found to be in good agreement with the experimental measurements of cluster growth when invoking a freeze-out temperature, and tempora...

Upon the occasion of the 500th anniversary Martin Luther’s publication of his 95 theses, this composite article brings together five perspectives on the missiological legacy of the reformer and the subsequent Protestant Reformation. The blend of voices makes clear that Luther and the subsequent Protestant Reformation do not have a simple missiological legacy but rather various legacies: theological, ecclesiological, political, and practical; some of which co-exist, and even collide, in the same ecclesiastical community. The scandalous legacy of a splintered and splintering church remains. Yet, demonstrations of mutual recognition, reciprocal respect, and genuine fellowship can be found in certain missiological circles.

This study aims to analyze the left ventricular function parameters, scar load, and hypertrophy in a mouse model of pressure-overload left ventricular (LV) hypertrophy over the course of 8 weeks using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) micro-positron emission tomography (microPET) imaging. LV hypertrophy was induced in C57BL/6 mice by transverse aortic constriction (TAC). Myocardial hypertrophy developed after 2–4 weeks. ECG-gated microPET scans with [18F]FDG were performed 4 and 8 weeks after surgery. The extent of fibrosis was measured by histopathologic analysis. LV function parameters and scar load were calculated using QGS®/QPS®. LV metabolic volume (LVMV) and percentage injected dose per gram were estimated by threshold-based analysis. The fibrotic tissue volume increased significantly from 4 to 8 weeks after TAC (​1.67 vs. 3.91 mm3; P = 0.044). There was a significant increase of the EDV (4 weeks: 54 ± 15 μl, 8 weeks: 79 ± 32 μl, P

Patients with pulmonary embolism who are in hemodynamically unstable condition present a special challenge to the interventionalist. When treating such patients, extracorporeal membranous oxygenation (ECMO) can help to stabilize these patients' condition; however, specific criteria for its use do not exist. Two patients are presented here to familiarize the reader with the use of ECMO and to demonstrate its utility for the interventional radiologist.

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience.

In Zeiten, in denen die Potenziale digital-befahigter Geschaftsmodellinnovationen noch uberwiegend ungenutzt sind, sehnt sich die Geschaftswelt nach einem neuen Typus kaufmannischer Geschaftsleitungen und Finanzvorstande. Unternehmenseigner und Aufsichtsrate fangen bereits an, ihre Anforderungsbeschreibungen der Rolle des Finanzvorstands/CFO oder kaufmannischen Geschaftsfuhrers zu uberdenken. Uberwiegend werden aber kaufmannische Leitungen heute noch in der Regel mehr daran gemessen, wie sie operative Funktionen ihres Verantwortungsbereichs steuern und optimieren, weniger daran, wie sie Wachstum, Innovation und Wiedererfindung ihres Unternehmens ermoglichen und treiben. Dies kaskadiert sich dann in die haufig vom CFO abhangigen Bereiche Finanzen, Controlling, Einkauf, Logistik, IT und in mittelstandischen Unternehmen auch haufig Personal. Transformationsprojekte in diesen Funktionen sind immer noch uberwiegend selbstzentriert und Transformationsansatze sind viel zu haufig auf Bewertungskriterien der 1980er Produktivitatswelle und der 1990er Cost-Cutting-Initiativen beschrankt. Beispielsweise haben es Einkaufer schwer, die mentalen Strasenbahnschienen des „Mehr fur Weniger“ zu verlassen und viele IT-Leiter vermogen immer noch nicht aus der Komfortzone des IT-Infrastruktur-, IT-Anwendungs- und IT-Servicemanagements auszubrechen. Viel zu haufig gibt es scheinbar weder Zeit oder Budget noch Anerkennung, sich auch in den vom CFO verantworteten Bereichen explorativ den Anforderungen an die Wiedererfindung von Unternehmens- und Betriebsmodellen durch Okosysteme, Plattformokonomien und Schnellskalierung zu widmen. Hier ist ein neuer Typus von kaufmannischer Geschaftsleitung gefragt, der „Digitalisierung“ nicht als begrenzte Anzahl von Einzellosungen und Leuchtturmprojekten versteht und diese nicht ausschlieslich nach Standard-RoI-Vorgaben beginnt, treibt und ggf. stoppt. Es wird vielmehr einen CFO gebraucht, der im Sparring mit dem CEO neue, erweiterte Ambitionen fur das Unternehmen ermoglicht sowie ein neutrales Verstandnis von Unternehmensrisikomanagement hat, das Chancen den gleichen Platz einraumt wie Bedrohungen.

Eine 65-jahrige Philippinin, wohnhaft in der Schweiz, wurde uns bei unklarem Entzundungszustand mit Fieber, Halsschmerzen, Myalgien im Schulter- und Beckenbereich und Schmerzen in beiden Knien zugewiesen.

Une patiente originaire des Philippines residant en Suisse nous a ete adressee en raison d’un etat inflammatoire de cause indeterminee avec de la fievre, des maux de gorge, des myalgies et des douleurs des genoux.

CME: Typhoid Fever - Clinical Manifestation, Diagnosis, Therapy and Prevention

Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that plays a key role in the regulation of the inflammatory pathway. While inhibition of TNFR1 has been the focus of many studies for the treatment of autoimmune diseases such as rheumatoid arthritis, activation of the receptor is important for the treatment of immunodeficiency diseases such as HIV and neurodegenerative diseases such as Alzheimer's disease where a boost in immune signaling is required. In addition, activation of other TNF receptors such as death receptor 5 or FAS receptor is important for cancer therapy. Here, we used a previously established TNFR1 fluorescence resonance energy transfer (FRET) biosensor together with a fluorescence lifetime technology as a high-throughput screening platform to identify a novel small molecule that activates TNFR1 by increasing inter-monomeric spacing in a ligand-independent manner. This shows that the conformational rearrangement of pre-ligand assembled receptor dimers can determine the activity of the receptor. By probing the interaction between the receptor and its downstream signaling molecule (TRADD) our findings support a new model of TNFR1 activation in which varying conformational states of the receptor act as a molecular switch in determining receptor function.

Impaired proteostasis has been linked to various diseases, whereas little is known about the impact of peripherally misfolded proteins on the brain. We here studied the brain of mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryABR120G). At baseline, the CryABR120G mice showed impaired cognitive and motor functions, aberrant protein aggregates, neuroinflammation, impaired blood-brain barrier, and reduced proteasome activity in the brain compared with their non-transgenic (Ntg) littermates. Ischemic stroke dramatically exacerbated these pathological alterations and caused more severe brain dysfunction in CryABR120G mice than in the Ntg mice. Intravenously injecting the exosomes isolated from CryABR120G mouse blood into wild-type mice caused the similar phenotypes seen from CryABR120G mice. Importantly, the CryABR120G protein showed the prion-like properties. These results suggest that peripherally misfolded proteins in the heart remotely disrupt brain function through prion-like neuropathology, which may represent an underappreciated mechanism underlying heart-brain crosstalk.

Ein 92-jahriger Patient wurde aufgrund einer Synkope notfallmassig zugewiesen. Seit einigen Tagen litt er ­zudem unter starker wassriger Diarrhoe und Bauchschmerzen.

Un patient âge de 92 ans a ete adresse au service des urgences en raison d’une syncope. Depuis quelques jours, il souffrait en outre d’une forte diarrhee aqueuse et de douleurs abdominales.

Arabidopsis Rubisco activase (Rca) is phosphorylated at threonine-78 (Thr78) in low light and in the dark, suggesting a potential regulatory role in photosynthesis, but this has not been directly tested. To do so, we transformed an rca-knockdown mutant largely lacking redox regulation with wild-type Rca-β or Rca-β with Thr78-to-Ala (T78A) or Thr78-to-Ser (T78S) site–directed mutations. Interestingly, the T78S mutant was hyperphosphorylated at the Ser78 site relative to Thr78 of the Rca-β wild-type control, as evidenced by immunoblotting with custom antibodies and quantitative mass spectrometry. Moreover, plants expressing the T78S mutation had reduced photosynthesis and quantum efficiency of photosystem II (ϕ(PSII)) and reduced growth relative to control plants expressing wild-type Rca-β under all conditions tested. Gene expression was also altered in a manner consistent with reduced growth. In contrast, plants expressing Rca-β with the phospho-null T78A mutation had faster photosynthetic induction kinetics and increased ϕ(PSII) relative to Rca-β controls. While expression of the wild-type Rca-β or the T78A mutant fully rescued the slow-growth phenotype of the rca-knockdown mutant grown in a square-wave light regime, the T78A mutants grew faster than the Rca-β control plants at low light (30 µmol photons m(−2) s(−1)) and in a fluctuating low-light/high-light environment. Collectively, these results suggest that phosphorylation of Thr78 (or Ser78 in the T78S mutant) plays a negative regulatory role in vivo and provides an explanation for the absence of Ser at position 78 in terrestrial plant species.