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In cardiac cine magnetic resonance imaging (MRI), the heart is repeatedly imaged at numerous time points during the cardiac cycle. Frequently, the temporal evolution of a certain region of interest such as the ventricles or the atria is highly relevant for clinical diagnosis. In this paper, we devise a novel approach that allows for an automatized propagation of an arbitrary region of interest (ROI) along the cardiac cycle from respective annotated ROIs provided by medical experts at two different points in time, most frequently at the end-systolic (ES) and the end-diastolic (ED) cardiac phases. At its core, a 3D TV- L 1 -based optical flow algorithm computes the apparent motion of consecutive MRI images in forward and backward directions. Subsequently, the given terminal annotated masks are propagated by this bidirectional optical flow in 3D, which results, however, in improper initial estimates of the segmentation masks due to numerical inaccuracies. These initially propagated segmentation masks are then refined by a 3D U-Net-based convolutional neural network (CNN), which was trained to enforce consistency with the forward and backward warped masks using a novel loss function. Moreover, a penalization term in the loss function controls large deviations from the initial segmentation masks. This method is benchmarked both on a new dataset with annotated single ventricles containing patients with severe heart diseases and on a publicly available dataset with different annotated ROIs. We emphasize that our novel loss function enables fine-tuning the CNN on a single patient, thereby yielding state-of-the-art results along the complete cardiac cycle.

Objective: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer., Methods: A clinical review based on current literature was generated by a multidisciplinary author panel., Results: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed., Conclusion: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer., Competing Interests: Disclosure Dr Nikiforov has IP ownership and receives royalties related to Thyroseq from the University of Pittsburgh as well as Consultancy agreement with Sonic Healthcare USA. Dr Randolph has received research grants (no personal fees) from Eisai, Medtronic and Fluoptics. Dr Randolph is the program director of the Mass. Eye & Ear Infirmary Endocrine Surgery Clinical Fellowship, which receives partial funding from Medtronic. Dr Randolph is the President of the International Thyroid Oncology Group (ITOG) and the World Congress on Thyroid Cancer (WCTC), is Chair of the Administrative Division of the American Head and Neck Society (AHNS) and is the American College of Surgeons (ACS) Otolaryngology Governor. All other authors have no conflicts to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Background: According to current estimates, the number of people needing care will double in the next 40 years. It is expected that between 130,000 and 190,000 additional nurses will be needed by 2030 in Germany. Physical and psychological burdens associated with nursing in long-term care facilities can develop into serious health risk factors and significantly impact occupational factors such as absenteeism, especially when linked to difficult working conditions. However, demands and resources specific to the nursing profession have not been analyzed extensively to preserve and promote nurses' workability and health adequately., Objective: Our study aimed to examine the extent to which perceived health among geriatric nursing staff in Germany is predicted by personal resources, job demands, and job resources. In addition, we analyzed the impact of different behavior and experience patterns on these relationships., Design, Setting, and Participants: An observational study was conducted between August 2018 and February 2020 in 48 nursing home facilities with 854 staff members in Germany as part of the project 'PROCARE - Prevention and occupational health in long-term care'., Methods: The survey contained instruments that measure workplace exposure, musculoskeletal complaints, physical and mental well-being, chronic stress, and work-related behavior and experience patterns. In addition, health-related information on physical activity and nutrition was collected. Data were analyzed using structural equation modeling., Results: The combined physical and mental workload for geriatric nurses is very high, with 75 % showing chronic stress. In the overall model, job and personal resources have a stronger association with mental health than physical health, while job demands have an equal impact on mental and physical health. Coping behavior also plays an important key role that should be assessed and considered. A behavior and experience risk pattern (health-endangering) is more strongly associated with a lower health status than a health-promoting behavior pattern. Results of the multigroup test showed that work-related behavior and experience patterns significantly moderate the relationship between physical health and mental health (χ 2  = 392/p ≤ .001/df = 256/RMSEA = 0.028/CFI = 0.958/TLI = 0.931). Only 43 % show a health-friendly coping pattern., Conclusions: Our findings underline the importance of holistic health promotion, which not only aims at changes at the behavioral level and the development of coping strategies but also takes on the task of reducing the workload and including measures to improve the working climate., Trial Registration Number: DRKS.de (DRKS00015241); August 9, 2018., Tweetable Abstract: Healthier coping patterns can benefit geriatric nurses' health. However, this is not a substitute for improving working conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: The exact role of portal hypertension in cirrhotic cardiomyopathy remains unclear, and it is uncertain whether cardiac abnormalities also occur in non-cirrhotic portal hypertension (NCPH). This magnetic resonance imaging (MRI) study aimed to evaluate the presence of subclinical myocardial dysfunction, oedema, and fibrosis in NCPH., Methods and Results: In this prospective study (2018-2022), participants underwent multiparametric abdominal and cardiac MRI including assessment of cardiac function, myocardial oedema, late gadolinium enhancement (LGE), and abdominal and cardiac mapping [T1 and T2 relaxation times, extracellular volume fraction (ECV)]. A total of 111 participants were included [44 participants with NCPH (48 ± 15 years; 23 women), 47 cirrhotic controls, and 20 healthy controls]. The cirrhotic group was dichotomized (Child A vs. Child B/C). NCPH participants demonstrated a more hyperdynamic circulation compared with healthy controls (cardiac index: 3.7 ± 0.6 vs. 3.2 ± 0.8 L/min/m², P = 0.004; global longitudinal strain: -27.3 ± 4.6 vs. -24.6 ± 3.5%, P = 0.022). The extent of abnormalities indicating myocardial fibrosis and oedema in NCPH was comparable with Child A cirrhosis (e.g. LGE presence: 32 vs. 33 vs. 69%, P = 0.004; combined T1 and T2 elevations: 46 vs. 27 vs. 69%, P = 0.017; NCPH vs. Child A vs. Child B/C). Correlations between splenic T1 and myocardial T1 values were found (r = 0.41; P = 0.007). Splenic T1 values were associated with the presence of LGE (odds ratio, 1.010; 95% CI: 1.002, 1.019; P = 0.013)., Conclusion: MRI parameters of myocardial fibrosis and oedema were altered in participants with NCPH to a similar extent as in compensated cirrhosis and were associated with splenic markers of portal hypertension, indicating specific portal hypertensive cardiomyopathy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background The objective of this study was to investigate cardiac abnormalities in intensive care unit (ICU) survivors of critical illness and to determine whether temporary acute kidney injury (AKI) is associated with more pronounced findings on cardiovascular magnetic resonance. Methods and Results There were 2175 patients treated in the ICU (from 2015 until 2021) due to critical illness who were screened for study eligibility. Post-ICU patients without known cardiac disease were prospectively recruited from March 2021 to May 2022. Participants underwent cardiovascular magnetic resonance including assessment of cardiac function, myocardial edema, late gadolinium enhancement, and mapping including extracellular volume fraction. Student t test, Mann-Whitney U test, and χ 2 tests were used. There were 48 ICU survivors (46±15 years of age, 28 men, 29 with AKI and continuous kidney replacement therapy, and 19 without AKI) and 20 healthy controls who were included. ICU survivors had elevated markers of myocardial fibrosis (T1: 995±31 ms versus 957±21 ms, P <0.001; extracellular volume fraction: 24.9±2.5% versus 22.8±1.2%, P <0.001; late gadolinium enhancement: 1% [0%-3%] versus 0% [0%-0%], P <0.001), more frequent focal late gadolinium enhancement lesions (21% versus 0%, P =0.03), and an impaired left ventricular function (eg, ejection fraction: 57±6% versus 60±5%, P =0.03; systolic longitudinal strain: 20.3±3.7% versus 23.1±3.5%, P =0.004) compared with healthy controls. ICU survivors with AKI had higher myocardial T1 (1002±33 ms versus 983±21 ms; P =0.046) and extracellular volume fraction values (25.6±2.6% versus 23.9±1.9%; P =0.02) compared with participants without AKI. Conclusions ICU survivors of critical illness without previously diagnosed cardiac disease had distinct abnormalities on cardiovascular magnetic resonance including signs of myocardial fibrosis and systolic dysfunction. Findings were more abnormal in participants who experienced AKI with necessity of continuous kidney replacement therapy during their ICU stay. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05034588.

A highly promising route to scale millions of qubits is to use quantum photonic integrated circuits (PICs), where deterministic photon sources, reconfigurable optical elements, and single-photon detectors are monolithically integrated on the same silicon chip. The isolation of single-photon emitters, such as the G centers and W centers, in the optical telecommunication O-band, has recently been realized in silicon. In all previous cases, however, single-photon emitters were created uncontrollably in random locations, preventing their scalability. Here, we report the controllable fabrication of single G and W centers in silicon wafers using focused ion beams (FIB) with high probability. We also implement a scalable, broad-beam implantation protocol compatible with the complementary-metal-oxide-semiconductor (CMOS) technology to fabricate single telecom emitters at desired positions on the nanoscale. Our findings unlock a clear and easily exploitable pathway for industrial-scale photonic quantum processors with technology nodes below 100 nm., (© 2022. The Author(s).)

Purpose: To evaluate cardiac MRI characteristics in patients with suspected hypersensitivity myocarditis following mRNA COVID-19 vaccination., Materials and Methods: Patients clinically suspected of acute myocarditis after COVID-19 vaccination were retrospectively analyzed and compared against a healthy control group. Cardiac MRI protocol included parameters such as T1 and T2 relaxation times, extracellular volume (ECV), T2 signal intensity ratio, and late gadolinium enhancement (LGE). Lymph node size was assessed in the patient group on the injection side. Student t-test, analyses of variance (ANOVA) with Tukey post-hoc test, and χ 2 test were used for statistical analysis., Results: 20 patients with clinically suspected post-vaccine myocarditis (28 ± 12 years; 12 men) and 40 controls (31 ± 11 years; 25 men) were evaluated. According to the 2018 Lake Louise criteria (LLC), patients with clinically suspected myocarditis were further subdivided into an LLC-positive group (n = 9) and an LLC-negative group (n = 11). The mean time of symptom onset after vaccination was 1.1 ± 1.2 days (LLC-positive) and 6.5 ± 9.2 days (LLC-negative). Group differences in inflammatory variables between myocarditis patients and control subjects were more pronounced in the LLC-positive group (e. g., T1 relaxation time: 1041 ± 61 ms [LLC positive] vs. 1008 ± 79 ms [LLC-negative] vs. 970 ± 25 ms [control]; p <.001; or T2 signal intensity ratio 2.0 ± 0.3 vs. 1.6 ± 0.3 [LLC-negative] and vs. 1.6 ± 0.3 [control], p = .012). LLC-positive patients were significantly faster in receiving an MRI after initial symptom onset (8.8 ± 6.1 days vs. 52.7 ± 33.4 days; p = .001) and had higher troponin T levels (3938 ± 5850 ng/l vs. 9 ± 11 ng/l; p <.001). LGE lesions were predominantly located at the subepicardium of the lateral wall. Axillary lymphadenopathy was more frequent in the LLC-positive group compared to the LLC-negative group (8/9 [89 %] vs. 0/11 [0 %], p < 0.001)., Conclusion: Vaccine-induced myocarditis should be considered in patients with acute symptom onset after mRNA vaccination, especially if elevated serum troponin T is observed. Imaging findings of vaccine-induced myocarditis are similar to virus-induced myocarditis, allowing for the use of the Lake Louise Criteria for diagnostic purposes., Key Points: · Vaccine-induced hypersensitivity myocarditis can be confirmed with cardiac MRI. · Especially patients with sudden onset of symptoms and elevated serum troponin T had positive cardiac MRI findings. · Cardiac MRI characteristics of vaccine-induced myocarditis are similar to those in virus-induced myocarditis., Citation Format: · Kravchenko D, Isaak A, Mesropyan N et al. Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination. Fortschr Röntgenstr 2022; 194: 1003 - 1011., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

High tibial osteotomy (HTO) represents a sensible treatment option for patients with moderate unicondylar osteoarthritis of the knee and extraarticular malalignment. The possibility of a continuously variable correction setting and a surgical approach low in complications has meant that the medial opening osteotomy has prevailed over the past decades. The objective of the present study was to determine whether anteromedially positioned small plates are nevertheless forgiving under biomechanically unfavourable conditions (overcorrection and lateral hinge fracture). In this study, a simulated HTO was performed on composite tibiae with a 10-mm wedge and fixed-angle anteromedial osteosynthesis with a small implant. Force was applied axially in a neutral mechanical axis, a slight and a marked overcorrection into valgus, with and without a lateral hinge fracture in each case. At the same time, a physiological gait with a dual-peak force profile and a peak load of 2.4 kN was simulated. Interfragmentary motion and rigidity were determined. The rigidity of the osteosynthesis increased over the cycles investigated. A slight overcorrection into valgus led to the lowest interfragmentary motion, compared with pronounced valgisation and neutral alignment. A lateral hinge fracture led to a significant decrease in rigidity and increase in interfragmentary motion. However, in no case was the limit of 1 mm interfragmentary motion critical for osteotomy healing exceeded. The degree of correction of the leg axis, and the presence of a lateral hinge fracture, have an influence on rigidity and interfragmentary motion. From a mechanically neutral axis ranging up to pronounced overcorrection, the implant investigated offers sufficient stability to allow healing of the osteotomy, even if a lateral hinge fracture is present.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

α-Isocyanoacetamide derivatives were first converted to oxazolines under newly developed conditions. These oxazolines were used as precursors of α-isocyanoacrylamides, which could lead to various 2-arylated imidazolones. In addition, it was shown that both oxazolines and their precursors could efficiently lead to imidazolones unsubstituted at C2 in a very rapid, one-pot transformation, thus paving the way toward unprecedented routes to imidazolones, having a good tolerance to different substitution patterns.

The secretion of recombinant proteins plays an important role in their economic production and purification. The secretion efficiency depends on the responsible signal peptide (SP) in combination with the target protein and the given host and cannot be predicted so far. Due to its high plasmid stability, the lack of alkaline extracellular proteases and only few contaminating extracellular host proteins, Priestia megaterium provides a promising alternative to common Bacillus species. For the development of an easy and fast cloning and screening system to identify the SP best suited to a distinct protein, a plasmid-based SP library containing all predicted 182 Sec-dependent SPs from P. megaterium was established. The splitting of the SPs into 10 groups of individual multi-SP plasmids (pMSPs) allows their grouped amplification and application in screening approaches. The functionality of the whole library was demonstrated by enhancing the amount of the already well-secreted α-amylase AmyE by 1.6-fold. The secretion of a novel penicillin G acylase, which remained as insoluble protein inside the cells, as its native SP is unsuitable for secretion in P. megaterium , could be enhanced even up to 29-fold. Overall, only around 170 recombinant P. megaterium clones based on 50 inserted SPs had to be screened to achieve sufficient amounts for further enzyme characterizations. Thus, this newly developed plasmid-based genetic tool applicable for P. megaterium and also other Bacillus species facilitates the identification of suitable SPs for secretion of recombinant proteins.

In the process of life course transitions, relations between the self and the world transform, which can according to Hartmut Rosa be framed as resonance. This article focuses on the retirement transition and thus on the exit from gainful employment as one of the central spheres of our world relationship in late modernity. It raises the following questions: How do experiences of resonance change in the course of the retirement transition? Does the loss of gainful employment lead to disruptions or even the absence of resonance in terms of alienation? And which role do dimensions of social inequality, such as gender, income, education or mental health status play for resonance transformations in the transition to retirement? In terms of a reflexive mixed-methods design, this article combines quantitative panel data from the German Ageing Survey (2008-17) with a qualitative longitudinal study from the project "Doing Retiring" (2017-21). Our results show that the transition from work to retirement entails a specific "resonance choreography" that comprises a phase of disaffection (lack of resonance) at the end of one's working life followed by a liminal phase in which people search for intensified experiences of resonance. We outline practices in which transitioning subjects seek out resonance, and the experiences they make within this process according to their social positions. We thereby find that the desire for resonance tends to be beyond intentional resonance management which manifests in products and services like coaching or wellness. In our conclusions, we discuss how resonance theory and retirement research/life course research can be fruitfully combined, but also highlight the methodological challenges the operationalization of resonance entails., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bischoff, Franke and Wanka.)

An unprecedented enantioselective conjugate addition reaction of sodium bisulfite to various nitrostyrenes occurred upon the influence of a bifunctional amino-thiourea organocatalyst; a strategy that opens a straightforward route to unprotected chiral taurine derivatives thanks to the reduction of the obtained β-nitroethanesulfonic acids into the corresponding amino derivatives.

We present a direct way to generate hillock-like nanostructures on CaF 2 (111) ionic crystals by kinetic energy deposition upon Au-cluster irradiation. In the past, the formation of similar nanostructures has been observed for both slow highly charged ions and swift heavy ions. However, in these cases, potential energy deposition of highly charged ions or the electronic energy loss of fast heavy ions, respectively, first leads to strong electronic excitation of the target material before the excitation energy is transferred to the lattice by efficient electron-phonon coupling. We now show that the kinetic energy deposited by slow single Au-clusters directly in the lattice of CaF 2 (111) leads to the production of nano-hillocks very similar to those found with slow highly charged and swift heavy ions, with heights between 1 and 2 nm. Our results are in good agreement with previous cluster irradiation studies regarding energy deposition and hence nano-structuring of surfaces, and we present Au-cluster irradiation as novel tool to fine-tune nanostructure formation., (Creative Commons Attribution license.)

While the application of focused ion beam (FIB) techniques has become a well-established technique in research and development for patterning and prototyping on the nanometer scale, there is still a large underused potential with respect to the usage of ion species other than gallium. Light ions in the range of m = 1-28 u (hydrogen to silicon) are of increasing interest due to the available high beam resolution in the nanometer range and their special chemical and physical behavior in the substrate. In this work, helium and neon ion beams from a helium ion microscope are compared with ion beams such as lithium, beryllium, boron, and silicon, obtained from a mass-separated FIB using a liquid metal alloy ion source (LMAIS) with respect to the imaging and milling resolution, as well as the current stability. Simulations were carried out to investigate whether the experimentally smallest ion-milled trenches are limited by the size of the collision cascade. While He + offers, experimentally and in simulations, the smallest minimum trench width, light ion species such as Li + or Be + from a LMAIS offer higher milling rates and ion currents while outperforming the milling resolution of Ne + from a gas field ion source. The comparison allows one to select the best possible ion species for the specific demands in terms of resolution, beam current, and volume to be drilled., (Copyright © 2020, Klingner et al.; licensee Beilstein-Institut.)

Single frequency, geometrically symmetric Radio-Frequency (rf) driven atmospheric pressure plasmas exhibit temporally and spatially symmetric patterns of electron heating, and consequently, charged particle densities and fluxes. Using a combination of phase-resolved optical emission spectroscopy and kinetic plasma simulations, we demonstrate that tailored voltage waveforms consisting of multiple rf harmonics induce targeted disruption of these symmetries. This confines the electron heating to small regions of time and space and enables the electron energy distribution function to be tailored.

The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma., (Copyright © 2018 by the National Comprehensive Cancer Network.)

For future nanoelectronic devices - such as room-temperature single electron transistors - the site-controlled formation of single Si nanocrystals (NCs) is a crucial prerequisite. Here, we report an approach to fabricate single Si NCs via medium-energy Si + or Ne + ion beam mixing of Si into a buried SiO 2 layer followed by thermally activated phase separation. Binary collision approximation and kinetic Monte Carlo methods are conducted to gain atomistic insight into the influence of relevant experimental parameters on the Si NC formation process. Energy-filtered transmission electron microscopy is performed to obtain quantitative values on the Si NC size and distribution in dependence of the layer stack geometry, ion fluence and thermal budget. Employing a focused Ne + beam from a helium ion microscope, we demonstrate site-controlled self-assembly of single Si NCs. Line irradiation with a fluence of 3000 Ne + /nm 2 and a line width of 4 nm leads to the formation of a chain of Si NCs, and a single NC with 2.2 nm diameter is subsequently isolated and visualized in a few nanometer thin lamella prepared by a focused ion beam (FIB). The Si NC is centered between the SiO 2 layers and perpendicular to the incident Ne + beam.

Objectives: Thyroglossal duct cyst (TGDC) is the most common congenital neck mass, presenting in up to 7% of the population. TGDC carcinoma is much less common, occurring in roughly 1% of patients diagnosed with TGDC. The vast majority of these tumors are papillary-type thyroid cancer. Given its rarity, there is wide variation in management recommendations for this disease. Extent of surgical management and need for adjuvant therapy including radioactive iodine ablation (RAI) are particularly debated, with some authors arguing aggressive therapy including RAI for any patients who undergo concurrent thyroidectomy with the Sistrunk procedure for TGDC carcinoma. We present a series of patients treated for TGDC carcinoma at our institutions and discuss our management algorithm., Methods: This is a retrospective chart review of patients with TGDC treated at 2 separate institutions. Factors reviewed included patient age, sex, preoperative diagnosis, preoperative work-up, extent of therapy, and use of adjuvant therapy., Results: Six patients who were treated for TGDC carcinoma at our institutions were identified. One patient was excluded because the patient had been treated at an outside facility prior to referral. All patients had papillary-type thyroid cancer. One patient underwent the Sistrunk procedure alone, and the remaining 4 underwent the Sistrunk procedure plus total thyroidectomy. Two of 4 patients were noted to have malignancy in the thyroid. Two of 4 patients who underwent thyroidectomy additionally received adjuvant RAI., Conclusion: Thyroglossal duct cyst carcinoma is uncommon and management is controversial. In low-risk patients (single tumor focus, negative margins, normal preoperative neck/thyroid imaging, no extension of TGDC carcinoma beyond the cyst wall), the Sistrunk procedure alone with observation of the thyroid may be sufficient. In this patient population, RAI is unlikely to be of any substantial benefit.

Introduction: The use of Kinesio tape (KT) to improve proprioception is a matter of considerable debate. In comparison, the rupture of the anterior cruciate ligament is a sufficiently well-investigated injury with a proven compromise of proprioception. The objective of the present study was to assess a supportive effect on proprioception after KT application, taking the anterior cruciate ligament (ACL) rupture as an example., Materials and Methods: Forty-eight patients who had suffered an ACL rupture, confirmed clinically and by magnetic resonance imaging, and who were treated conservatively or were awaiting surgery were included in this study. In all patients, a gait analysis was performed on the affected leg before and after KT application. In addition, the IKDC score, the Lysholm score, stability using the Rolimeter, and the angle reproduction test were determined., Results: Thirty-nine men and nine women who had had an ACL rupture for at least 3 weeks were included in the study. Significant improvements were achieved on the affected knee joint for the gait analysis parameters touchdown and unrolling, cadence, stability and stance phase as well as an extension of the hip joint. The Lysholm score improved from 79.3 to 85.8 (p < 0.001) and the IKDC score from 60.2 to 71.3 points (p < 0.001). Significant improvements were achieved in the Rolimeter and angle reproduction test., Conclusions: The use of KT has a positive effect on proprioception in patients with an anterior cruciate ligament rupture. Therefore, the application may improve gait pattern as well as the subjective function of the affected knee joint.

A series of hydroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 carbon atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hydroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'., (© 2018 The Author(s).)

Electronic skins equipped with artificial receptors are able to extend our perception beyond the modalities that have naturally evolved. These synthetic receptors offer complimentary information on our surroundings and endow us with novel means of manipulating physical or even virtual objects. We realize highly compliant magnetosensitive skins with directional perception that enable magnetic cognition, body position tracking, and touchless object manipulation. Transfer printing of eight high-performance spin valve sensors arranged into two Wheatstone bridges onto 1.7-μm-thick polyimide foils ensures mechanical imperceptibility. This resembles a new class of interactive devices extracting information from the surroundings through magnetic tags. We demonstrate this concept in augmented reality systems with virtual knob-turning functions and the operation of virtual dialing pads, based on the interaction with magnetic fields. This technology will enable a cornucopia of applications from navigation, motion tracking in robotics, regenerative medicine, and sports and gaming to interaction in supplemented reality.

Recently developed laser-based measurement techniques are used to image the temperatures and velocities in gas flows. They require new phosphor materials with an unprecedented combination of properties. A novel synthesis procedure is described here; it results in hierarchically structured, hollow microspheres of Eu 3+ -doped Y 2 O 3 , with unusual particle sizes and very good characteristics compared to full particles. Solution-based precipitation on polymer microballoons produces very stable and luminescent, ceramic materials of extremely low density. As a result of the - compared to established template-directed syntheses - reduced mass of polymer that is lost upon calcination, micron-sized particles are obtained with mesoporous walls, low defect concentrations, and nanoscale wall thicknesses. They can be produced with larger diameters (~25 µm) compared to known hollow spheres and exhibit an optimized flow behavior. Their temperature sensing properties and excellent fluidic follow-up behavior are shown by determining emission intensity ratios in a specially designed heating chamber. Emission spectroscopy and imaging, electron microscopy and X-ray diffraction results are presented for aerosolizable Y 2 O 3 with an optimized dopant concentration (8%). Challenges in the field of thermofluids can be addressed by combined application of thermometry and particle image velocimetry with such hollow microparticles.

High current liquid metal ion sources are well known and found their first application as field emission electric propulsion thrusters in space technology. The aim of this work is the adaption of such kind of sources in broad ion beam technology. Surface patterning based on self-organized nano-structures on, e.g., semiconductor materials formed by heavy mono- or polyatomic ion irradiation from liquid metal (alloy) ion sources (LMAISs) is a very promising technique. LMAISs are nearly the only type of sources delivering polyatomic ions from about half of the periodic table elements. To overcome the lack of only very small treated areas by applying a focused ion beam equipped with such sources, the technology taken from space propulsion systems was transferred into a large single-end ion implanter. The main component is an ion beam injector based on high current LMAISs combined with suited ion optics allocating ion currents in the μA range in a nearly parallel beam of a few mm in diameter. Different types of LMAIS (needle, porous emitter, and capillary) are presented and characterized. The ion beam injector design is specified as well as the implementation of this module into a 200 kV high current ion implanter operating at the HZDR Ion Beam Center. Finally, the obtained results of large area surface modification of Ge using polyatomic Bi 2 + ions at room temperature from a GaBi capillary LMAIS will be presented and discussed.

Crystalline and preamorphized isotope multilayers are utilized to investigate the dependence of ion beam mixing in silicon (Si), germanium (Ge), and silicon germanium (SiGe) on the atomic structure of the sample, temperature, ion flux, and electrical doping by the implanted ions. The magnitude of mixing is determined by secondary ion mass spectrometry. Rutherford backscattering spectrometry in channeling geometry, Raman spectroscopy, and transmission electron microscopy provide information about the structural state after ion irradiation. Different temperature regimes with characteristic mixing properties are identified. A disparity in atomic mixing of Si and Ge becomes evident while SiGe shows an intermediate behavior. Overall, atomic mixing increases with temperature, and it is stronger in the amorphous than in the crystalline state. Ion-beam-induced mixing in Ge shows no dependence on doping by the implanted ions. In contrast, a doping effect is found in Si at higher temperature. Molecular dynamics simulations clearly show that ion beam mixing in Ge is mainly determined by the thermal spike mechanism. In the case of Si thermal spike, mixing prevails at low temperature whereas ion beam-induced enhanced self-diffusion dominates the atomic mixing at high temperature. The latter process is attributed to highly mobile Si di-interstitials formed under irradiation and during damage annealing., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Objectives: The aim of this study was to analyze whether health-related characteristics of elderly differ considering their income situation., Methods: N=322 elderly were included in a quantitative survey (e. g., SF36, GDS, Barthelindex, IADL). The evaluation was conducted in consideration of housing (independent, outpatient, nursing homes, district)., Results: There were significantly higher values of diseases in the lower income than in higher income groups (F(316)=2,971; p=0,008; eta²=0,053). Furthermore the lower income groups were more often classified into long-term care level 2 (Chi²=25,36; p=0,009; C=0,283) associated with reduced abilities of daily living and lower scores on physical and mental wellbeing. Gender differences could not be found., Conclusions: Low-income elderly have a poorer health status than high-income elderly. Endeavors should be undertaken to improve prevention strategies to retain independence and quality of life of low-income elderly., (© Georg Thieme Verlag KG Stuttgart · New York.)

We introduce droplet-confined alternate pulsed epitaxy for the self-catalyzed growth of GaAs nanowires on Si(111) substrates in the temperature range from 550 °C down to 450 °C. This unconventional growth mode is a modification of the migration-enhanced epitaxy, where alternating pulses of Ga and As4 are employed instead of a continuous supply. The enhancement of the diffusion length of Ga adatoms on the {11̅0} nanowire sidewalls allows for their targeted delivery to the Ga droplets at the top of the nanowires and, thus, for a highly directional growth along the nanowire axis even at temperatures as low as 450 °C. We demonstrate that the axial growth can be simply and abruptly interrupted at any time without the formation of any defects, whereas the growth rate can be controlled with high accuracy down to the monolayer scale, being limited only by the stochastic nature of nucleation. Taking advantage of these unique possibilities, we were able to probe and describe quantitatively the population dynamics of As inside the Ga droplets in specially designed experiments. After all, our growth method combines all necessary elements for precise growth control, in-depth investigation of the growth mechanisms and compatibility with fully processed Si-CMOS substrates.

The first one-pot synthesis of N-substituted 2-H-4-benzylidene imidazolones and their subsequent palladium-catalyzed and copper-assisted direct C2-H arylation and alkenylation with aryl- and alkenylhalides are described. This innovative synthesis is step-economical, azide-free, high yielding, highly flexible in the introduction of a variety of electronically different groups, and can be operated on large-scale. Moreover, the method allows direct access to C2-arylated or alkenylated imidazolone-based green fluorescent protein (GFP) and Kaede protein fluorophores, including ortho-hydroxylated models., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Empathy is an important human ability associated with successful social interaction. It is currently unclear how to optimally measure individual differences in empathic processing. Although the Big Five model of personality is an effective model to explain individual differences in human experience and behavior, its relation to measures of empathy is currently not well understood. Therefore, the present study was designed to investigate the relationship between the Big Five personality concept and two commonly used measures for empathy [Empathy Quotient (EQ), Interpersonal Reactivity Index (IRI)] in four samples from China, Germany, Spain, and the United States of America. This approach was designed to advance the way the Big Five personality model can be used to measure empathy. We found evidence of medium effect sizes for associations between personality and empathy, with agreeableness and conscientiousness as the most important predictors of affective and cognitive empathy (measured by the respective IRI subscales) as well as for a one-dimensional empathy score (measured by the EQ). Empathy in a fictional context was most closely related to openness to experience while personal distress was first of all related to neuroticism. In terms of culture, we did not observe any distinct pattern concerning cultural differences. These results support the cross-cultural applicability of the EQ and the IRI and indicate structurally similar associations between personality and empathy across cultures.

Nanomagnets form the building blocks for a variety of spin-transport, spin-wave and data storage devices. In this work we generated nanoscale magnets by exploiting the phenomenon of disorder-induced ferromagnetism; disorder was induced locally on a chemically ordered, initially non-ferromagnetic, Fe60Al40 precursor film using  nm diameter beam of Ne(+) ions at 25 keV energy. The beam of energetic ions randomized the atomic arrangement locally, leading to the formation of ferromagnetism in the ion-affected regime. The interaction of a penetrating ion with host atoms is known to be spatially inhomogeneous, raising questions on the magnetic homogeneity of nanostructures caused by ion-induced collision cascades. Direct holographic observations of the flux-lines emergent from the disorder-induced magnetic nanostructures were made in order to measure the depth- and lateral- magnetization variation at ferromagnetic/non-ferromagnetic interfaces. Our results suggest that high-resolution nanomagnets of practically any desired 2-dimensional geometry can be directly written onto selected alloy thin films using a nano-focussed ion-beam stylus, thus enabling the rapid prototyping and testing of novel magnetization configurations for their magneto-coupling and spin-wave properties.

At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

A microwave-assisted method for the palladium-catalyzed direct arylation of quinazolin-4-one has been developed under copper-assistance. This method is applicable to a wide range of aryl iodides and substituted (2H)-quinazolin-4-ones. This protocol provides a simple and efficient way to synthesize biologically relevant 2-arylquinazolin-4-one backbones.

Autoimmune destruction of insulin-producing β cells in type 1 diabetes and islet transplantation involves a variety of immune pathways but is primarily mediated by self-reactive T cells. Chemokines can modulate local immune responses in inflammation and tumors by recruiting immune cells. We have reported that expression of the chemokine CCL22 in pancreatic β cells in the NOD mouse prevents autoimmune attack by recruiting T regulatory cells (Tregs), protecting mice from diabetes. In this study we show that invariant NKT cells are also recruited to CCL22-expressing islet transplants and are required for CCL22-mediated protection from autoimmunity. Moreover, CCL22 induces an influx of plasmacytoid dendritic cells, which correlates with higher levels of IDO in CCL22-expressing islet grafts. In addition to its chemotactic properties, we found that CCL22 activates Tregs and promotes their ability to induce expression of IDO by dendritic cells. Islet CCL22 expression thus produces a tolerogenic milieu through the interplay of Tregs, invariant NKT cells, and plasmacytoid dendritic cells, which results in suppression of effector T cell responses and protection of β cells. The immunomodulatory properties of CCL22 could be harnessed for prevention of graft rejection and type 1 diabetes as well as other autoimmune disorders., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Direct C-H arylation and alkenylation of 4,4'-dialkylimidazolones with a broad range of halides under palladium and copper catalysis have been developed. This methodology is applied to the preparation of recently discovered fatty acid synthetase (FAS) inhibitors.

Manipulation of regulatory T cell (Treg) migration by islet expression of the chemokine CCL22 prevents diabetes in NOD mice and delays recurrent autoimmunity in syngeneic islet transplants. We sought to determine whether attracting Tregs with CCL22 also prevents islet allograft rejection. Isolated Bl/6 mouse islets were transduced overnight with adenovirus expressing CCL22 (Ad-CCL22) downstream of the CMV promoter. Islets were transplanted under the renal capsule of Balb/c recipients made diabetic by streptozotocin. To assess immunologic tolerance, graft-bearing kidneys from recipients of CCL22-expressing islet grafts were removed, and mice received a second transplant of naive islets from the same donor strain or third-party islets into the contralateral kidney. Adenoviral expression of CCL22 conferred prolonged protection of islet allografts in MHC-mismatched, diabetic recipients, maintaining normoglycemia in 75% of recipients for at least 80 days. Increased frequency of Treg cells was observed in islet grafts transduced with Ad-CCL22 compared with untreated grafts. Normoglycemic recipients of CCL22-expressing islet grafts showed complete absence of antidonor antibodies and no lymphocyte proliferation after exposure to donor splenocytes. After removal of the primary graft at day 80, mice that received a second transplant with untreated islets from the same donor strain did not reject the grafts, suggesting the development of tolerance. Expression of CCL22 recruits Treg cells to transplanted islets, prevents activation of alloreactive T-cells and islet allograft failure and induces alloantigen-specific tolerance. Manipulation of Treg cells by CCL22 in transplanted islets may be a novel therapeutic strategy for diabetes.

Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC) adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2), thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation.

The integration of most membrane proteins into the cytoplasmic membrane of bacteria occurs co-translationally. The universally conserved YidC protein mediates this process either individually as a membrane protein insertase, or in concert with the SecY complex. Here, we present a structural model of YidC based on evolutionary co-variation analysis, lipid-versus-protein-exposure and molecular dynamics simulations. The model suggests a distinctive arrangement of the conserved five transmembrane domains and a helical hairpin between transmembrane segment 2 (TM2) and TM3 on the cytoplasmic membrane surface. The model was used for docking into a cryo-electron microscopy reconstruction of a translating YidC-ribosome complex carrying the YidC substrate FOc. This structure reveals how a single copy of YidC interacts with the ribosome at the ribosomal tunnel exit and identifies a site for membrane protein insertion at the YidC protein-lipid interface. Together, these data suggest a mechanism for the co-translational mode of YidC-mediated membrane protein insertion., (Copyright © 2014, Wickles et al.)

The biogenesis of polytopic membrane proteins occurs co-translationally on ribosomes that are tightly bound to a membrane-embedded protein-conducting channel: the Sec-complex. The path that is followed by nascent proteins inside the ribosome and the Sec-complex is relatively well established; however, it is not clear what the fate of the N-terminal transmembrane domains (TMDs) of polytopic membrane proteins is when the C-terminal TMDs domains are not yet synthesized. Here, we present the sub-nanometer cryo-electron microscopy structure of an in vivo generated ribosome-SecY complex that carries a membrane insertion intermediate of proteorhodopsin (PR). The structure reveals a pre-opened Sec-complex and the first two TMDs of PR already outside the SecY complex directly in front of its proposed lateral gate. Thus, our structure is in agreement with positioning of N-terminal TMDs at the periphery of SecY, and in addition, it provides clues for the molecular mechanism underlying membrane protein topogenesis.

Tumor hypoxia plays a major role in reducing the efficacy of therapeutic modalities like chemotherapy and radiation therapy in combating cancer. In order to target hypoxic tissues, a tripeptide ligand having a 2-nitroimidazole moiety, as a bioreductive species, was synthesized. The latter was radiolabeled with (99m)Tc for imaging hypoxic regions of tumors and was characterized by means of its rhenium analogue. The biodistribution and scintigraphic image of the corresponding (99m)Tc-complex showed accumulation in tumor and these results suggest that it could be a marker for imaging tumor hypoxia., (Published by Elsevier Ltd.)

The syntheses of new nitroimidazole compounds using silicon-[(18)F]fluorine chemistry for the potential detection of tumor hypoxia are described. [(18)F]silicon-based compounds were synthesized by coupling 2-nitroimidazole with silyldinaphtyl or silylphenyldi-tert-butyl groups and labeled by fluorolysis or isotopic exchange. Dinaphtyl compounds (6, 10) were labeled in 56-71% yield with a specific activity of 45 GBq/μmol, however these compounds ([(18)F]7 and [(18)F]11) were not stable in plasma. Phenyldi-tert-butyl compounds were labeled in 70% yield with a specific activity of 3 GBq/μmol by isotopic exchange, or in 81% yield by fluorolysis of siloxanes with a specific activity of 45 GBq/μmol. The labeled compound [(18)F]18 was stable in plasma and excreted by the liver and kidneys in vivo. In conclusion, the fluorosilylphenyldi-tert-butyl (SiFA) group is more stable in plasma than fluorosilyldiphenyl moiety. Thus, compound [(18)F]18 is suitable for further in vivo assessments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Starting from alkyl halides or Michael acceptors, thioacetates were prepared in situ and further treated with t-BuOCl, affording the corresponding sulfonyl chlorides which were trapped with nucleophiles such as water, alcohol, or amines. The three steps can be achieved in a one-pot procedure. Oxidative deprotection also proved to be efficient with S-trityl and S-tert-butyl groups, making it a convenient route toward cysteic acid derivatives.

Due to their reduced dimensions, the mechanical properties of nanostructures may differ substantially from those of bulk materials. Quantifying and understanding the nanomechanical properties of individual nanostructures is thus of tremendous importance both from a fundamental and a technological point of view. Here we employ a recently introduced atomic force microscopy mode, i.e., peak-force quantitative nanomechanical imaging, to map the local elastic properties of nanostructured germanium surfaces. This imaging mode allows the quantitative determination of the Young's modulus with nanometer resolution. Heavy-ion irradiation was used to fabricate different self-organized nanostructures on germanium surfaces. Depending on the sample temperature during irradiation, nanoporous sponge-like structures and hexagonally ordered nanodots are obtained. The sponge-like germanium surface is found to exhibit a surprisingly low Young's modulus well below 10 GPa, which furthermore depends on the ion energy. For the nanodot patterns, local variations in the Young's modulus are observed: at moderate sample temperatures, the dot crests have a lower modulus than the dot valley whereas this situation is reversed at high temperatures. These observations are explained by vacancy dynamics in the amorphous germanium matrix during irradiation. Our results furthermore offer the possibility to tune the local elastic properties of nanostructured germanium surfaces by adjusting the ion energy and sample temperature.

A new method for the fabrication of spherical gallium nanoparticles (Ga-NPs) on diamond-like carbon (DLC) layers with high precision in their desired diameter and positioning is presented. The basic principle is the pre-patterning of a DLC film by focused Ga(+) ion beam irradiation and subsequent annealing. During thermal treatment the evolution of single Ga-NPs with spherical shape on irradiated areas is driven by phase separation and surface segregation of Ga from the supersaturated DLC layer. The shape and size of the implanted areas as well as the ion fluence serve as a Ga reservoir for the nanoparticle (NP) evolution which is strongly correlated with the NP diameter. For the formation of segregation seeds to avoid random segregation of the NPs small spots are additionally implanted with Ga within the irradiated areas. The NP evolution is then assessed with respect to the seed position and the material for the Ga-NP growth is gathered from the surrounding reservoir. Using this technique Ga-NPs were fabricated with a diameter ranging from 40 nm up to several hundred nm. Prospective applications, i.e. in the field of plasmonics, arise from the arrangement in chains as well as in periodical two-dimensional arrays with defined NP size and interparticle distance.

We have carried out a series of measurements demonstrating the feasibility of using the Dresden electron beam ion source (EBIS)-A, a table-top sized, permanent magnet technology based electron beam ion source, as a charge breeder. Low charged gold ions from an AuGe liquid metal alloy ion source were injected into the EBIS and re-extracted as highly charged ions, thereby producing charge states as high as Au(60 +). The setup, the charge breeding technique, breeding efficiencies as well as acceptance and emittance studies are presented.

Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the CD4+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells and CD8+ IFN-γ–producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes.

Starting from amino acid esters, new peptidomimetics based on the imidazole scaffold were prepared. An efficient and rapid sequence consisting of two subsequent one-pot procedures was developed and applied to various aminoacids. As they provide more substitution patterns, these heterocyclic mimics are promising tools for structural and biological studies.

This study evaluated simple procedures for GFR determination in 48 liver-transplanted children. After injection of (51)Cr-EDTA, blood samples were obtained up to four h, and activity retention in the body was measured for 60 min with scintillation probes. As a reference, GFR was calculated according to Sapirstein. Simplified calculations were performed according to Brochner-Mortensen, Russel, Devaux and Oberhausen. Additionally, GFR was determined using plasma creatinine and cystatin C according to Schwartz and Filler, respectively. The reference revealed mildly reduced GFR (62 +/- 20 mL/min/1.73 m(2)). Russel's method provided the highest degree of correlation (r(2) = 0.95), the smallest bias in GFR determination (-2%), and only one false exclusion plus one false diagnosis of chronic kidney disease. Oberhausen's method with blood sampling at one h post-injection performed slightly worse (r(2) = 0.67, bias: 3%). All other methods resulted in significantly different GFR estimates compared to the reference. Nevertheless, notably, the second narrowest 95% limits of agreement (-31% to 45%) was observed using cystatin C. In conclusion, this data implies to prefer Russel's method as a simplified procedure, and if patients cannot be available long enough (four h) for measurements, Oberhausen's method instead. If radiotracer methods are not available at all or for screening GFR, cystatin C appears to be the procedure of choice.

IL-1R antagonist (IL-1Ra) is a natural inhibitor of the pleiotropic proinflammatory activities of IL-1. Although several reports described the effects of complete IL-1Ra deficiency, no study has examined the consequences of cell type-specific IL-1Ra inactivation during systemic inflammation. Previous in vitro data demonstrated high IL-1Ra production by hepatocytes and myeloid cells after endotoxin stimulation. In addition, hepatocyte IL-1Ra production is regulated as an acute-phase protein in vitro. In this study, we analyzed the production and functional role of hepatocyte- and myeloid cell-derived IL-1Ra during endotoxin-induced septic shock and acute IL-1beta-induced sterile inflammation. Using conditional IL-1Ra knockout mice, we showed that hepatocytes and myeloid cells are the two major cellular sources of circulating IL-1Ra in response to LPS. Interestingly, IL-1Ra production by myeloid cells, but not hepatocytes, is critical for survival during endotoxemia. Furthermore, we provide the first in vivo evidence demonstrating that IL-1Ra is produced as an acute-phase protein by hepatocytes during IL-1beta-induced inflammation and that hepatocyte-derived IL-1Ra functions as an endogenous negative feedback downregulating the proinflammatory effects of IL-1. Taken together, our observations define distinct roles for two major cellular sources of IL-1Ra in response to different types of systemic inflammatory stimuli in vivo.