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Therapies of head and neck squamous cell carcinoma (HNSCC), particularly irradiation and chemotherapy (C/RT), can affect salivary glands to some extent. Recent studies suggest that point shear wave elastography (pSWE) is well suited for the diagnosis and rating of homogenous damage to parenchymatous organs. The purpose of this study was to assess the value of this sonographic modality as a tool for the evaluation both of salivary gland affection after HNSCC therapy and the effect of a salivary replacement therapy based on liposomes. A total of 69 HNSCC patients were included in this study. All patients had finished cancer treatment and attended regular follow-up. pSWE values of ipsi- and contralateral parotid (PG) and submandibular glands (SMG) were obtained in a standardized manner and compared to those of a healthy control (HC) group. After a two months treatment with a liposomal saliva replacement therapy pSWE quantification was performed again. Ipsi- and contralateral salivary glands suffer under standard HNSCC tumor therapy. Here, the ipsilateral parotid gland (PG) is primarily affected. Therefore, a sequence of manifestation (surgery < surgery plus adjuvant C/RT < primary C/RT) is comprehensible, evaluated by pSWE measurements. The examination of all glands and statistical analysis of the values compared to controls resulted in an pSWE cutoff value for affected glandular tissue of >2 m/s. Using a liposomal saliva replacement therapy, pSWE values of the ipsilateral PG can be improved, although the level of HC could not be restored. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study is to measure the motor development and tracking of physical fitness (PF) components of primary school children of Trier in Germany. Methods. Two longitudinal cohorts, of 1768 children (915 f, 853 m) aged 5–11, were measured. In longitudinal cohort 1, a total of 116 female and 137 male participants aged 6.80±0.42 years at baseline were measured four times from grade 1 to grade 4 (response: 40.4%). Participants of longitudinal cohort 2 (166 f, 149 m; 6.70±0.36 years at baseline, response: 42.6%) were examined three times from grade 1 to grade 3 with the German Motor Test 6–18 (DMT 6–18). Results. Physical fitness increased significantly over time in all test tasks except flexibility. Gender-specific differences were found in 20 m sprint, 6-minute run, balancing backwards, jumping sideways, and stand and reach. 74.4% of PF stability coefficients were moderate (r=0.30 to 0.60). Stability of PF declined with increased time frames. Tracking was lower in girls than in boys. Flexibility showed the highest stability among PF variables (r > 0.50). BMI showed the overall highest stability coefficient with r > 0.7. Conclusions. Gender-specific differences of PF were obvious but cannot always be secured statistically in primary school. Tracking was only moderate. Variability in the timing and speed of the adolescent growth spurt and sexual maturation influence stability of PF. Results from longitudinal cohort 2 largely confirm those from longitudinal cohort 1. [ABSTRACT FROM AUTHOR]

A method for monitoring hemodialysis based on quantitative infrared spectroscopic determination of the molecules dialyzed from patient blood is reported. The measurements are reagent-free and aim at real-time and in-line monitoring of the hemodialysis patient. A flow cell using attenuated total reflection infrared spectroscopy is coupled downstream of the dialysis filter unit. A calibration model has been developed from real hemodialysis samples analyzed by chemical reference analysis and from artificially mixed dialysis samples. The infrared monitoring of hemodialysis includes quantitative determination of urea as the lead substance, as well as glucose, lactate, and creatinine, all at a precision only limited by the chemical reference analysis. The flow cell can be fitted to all standard hemodialysis systems. Preliminary tests with hemodialysis patients have demonstrated that detoxification can be clearly monitored. Furthermore, these experiments demonstrate that a wide, real-time control of the patient's physiological parameters is possible with this method, which could lead to increased patient safety. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The prediction and experimental verification of the quantum spin Hall state marked the discovery of a new state of matter now known as topological insulators. Two-dimensional topological insulators exhibit the quantum spin-Hall effect, characterized by gapless spin-polarized counter-propagating edge channels. Whereas the helical character of these edge channels is now well established, experimental confirmation that the transport in the edge channels is spin polarized is still outstanding. We report experiments on nanostructures fabricated from HgTe quantum wells with an inverted band structure, in which a split gate technique allows us to combine both quantum spin Hall and metallic spin Hall transport in a single device. In these devices, the quantum spin Hall effect can be used as a spin current injector and detector for the metallic spin Hall effect, and vice versa, allowing for an all-electrical detection of spin polarization. [ABSTRACT FROM AUTHOR]

Background: The LightCycler® Mycobacterium Detection Kit based on real-time PCR technology for the detection of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii was recently developed. This study evaluated its analytical sensitivity, specificity and reproducibility. Methodology/Principal Findings: Plasmid standards were prepared and used to determine the limit of detection. The assay was also performed against organisms other than mycobacteria, other mycobacterial strains and interfering substances to exclude cross-reactivity and interference. Reference standards were prepared and tested to assess the assay's reproducibility. All PCR assays were performed using the LightCycler® 2.0 Instrument. The detection limit for M. tuberculosis was 28 copies per microlitre. Neither cross-reactivity nor interference occurred with non-mycobacterial organisms and substances tested. Overall reproducibility for consecutive measurements, run-to-run, lot-to-lot, day-to-day and laboratoryto- laboratory achieved a coefficient of variance of less than two percent. Significance: The LightCycler® Mycobacterium Detection kit has shown to be a robust and accurate assay with the potential to be used as a rapid TB diagnostic test. [ABSTRACT FROM AUTHOR]

A comprehensive approach of bioprocess design at various levels was used to optimize microbial production of extracellular fructofuranosidase, important as biocatalyst to derive fructooligosaccharides with broad application in food or pharmaceutical industry. For production, the recombinant strain Aspergillus niger SKAn1015 was used, which expresses the fructofuranosidase encoding gene suc1 under control of a strong constitutive promoter. In a first screening towards an optimized medium, glucose, nitrate, Fe2+, and Mn2+ were identified as beneficial for production. A minimal medium with optimized concentration of these key nutrients, obtained by central composite design experiments and quadratic modelling, provided a threefold increased fructofuranosidase activity in the culture supernatant (400 U/mL) as compared to the originally described medium. Utilizing the optimized medium, the process was then transferred from shake flask into a fed-batch-operated bioreactor. Hereby, the intended addition of talc microparticles allowed engineering the morphology of A. niger into a highly active mycelial form, which strongly boosted production. Fructofuranosidase production was highly specific as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The secreted enzyme activity of 2,800 U/mL, corresponding to about 3 g/L of fructofuranosidase, achieved by the microparticle-enhanced fed-batch process, is tenfold higher than that of any other process reported so far, so that the presented bioprocess strategy appears as a milestone towards future industrial fructofuranosidase production. [ABSTRACT FROM AUTHOR]

Abstract: The cellular automata (CA) model is an important tool in land use studies. Scale is a central concept in both land use research and CA models. To better understand the connection between different scales and processes of land use change, more studies on the behavior of a CA model at different scales are necessary and urgent. The objective of this study was to explore the impact of variation in scale on the behavior of a CA employed for land use change modeling. The scale variation was represented by the variation in the spatial extent of the images used, in the cell size and in the neighborhood configuration, including the size and shape. Two aspects of the behavior of the model were examined: the algorithms expressing the land use transitions, and the precision of the model’s output. The average enrichment factor, which generates the transition rules, was used to quantify the interpretation of the land use transitions. The kappa index was used to quantify the precision of the model’s output. The results showed that the variation of the spatial extent, cell size, and neighborhood size and shape influenced the model’s behavior in different ways. A combination of small cell size and small neighborhood size generated improper expressions of the land use transitions. Here, we believe that an increase in the neighborhood size might be the solution. However, the precision of the simulation decreased when the neighborhood size increased with ring shape. In addition, the precision first increased and then decreased once the neighborhood size reached a certain value for a scope-shaped neighborhood. Based on these results, we recommend the finest resolution and a neighborhood size of 9×9 cells arranged in a scope shape. This set of parameters reflects the most accurate land information. The model interprets well the land use transitions that are identical to those found in actual “real” land transitions and also provides high-precision outputs. For different model applications at different spatial scales, a preliminary discussion of the scale parameter setting is recommended. [Copyright &y& Elsevier]

A set of different integrative expression vectors for the intracellular production of recombinant proteins with or without affinity tag in Aspergillus niger was developed. Target genes can be expressed under the control of the highly efficient, constitutive pkiA promoter or the novel sucrose-inducible promoter of the β-fructofuranosidase ( sucA) gene of A. niger in the presence or absence of alternative carbon sources. All expression plasmids contain an identical multiple cloning sequence that allows parallel construction of N- or C-terminally His6- and StrepII-tagged versions of the target proteins. Production of two heterologous model proteins, the green fluorescence protein and the Thermobifida fusca hydrolase, proved the functionality of the vector system. Efficient production and easy detection of the target proteins as well as their fast purification by a one-step affinity chromatography, using the His6- or StrepII-tag sequence, was demonstrated. [ABSTRACT FROM AUTHOR]

Nonlocal transport through edge channels holds great promise for low-power information processing. However, edge channels have so far only been demonstrated to occur in the quantum Hall regime, at high magnetic fields. We found that mercury telluride quantum wells in the quantum spin Hall regime exhibit nonlocal edge channel transport at zero external magnetic field. The data confirm that the quantum transport through the (helical) edge channels is dissipationless and that the contacts lead to equilibration between the counterpropagating spin states at the edge. The experimental data agree quantitatively with the theory of the quantum spin Hall effect. The edge channel transport paves the way for a new generation of spintronic devices for Jew-power information processing. [ABSTRACT FROM AUTHOR]

Summary: Antiviral immunity is triggered by immunorecognition of viral nucleic acids. The cytosolic helicase RIG-I is a key sensor of viral infections and is activated by RNA containing a triphosphate at the 5′ end. The exact structure of RNA activating RIG-I remains controversial. Here, we established a chemical approach for 5′ triphosphate oligoribonucleotide synthesis and found that synthetic single-stranded 5′ triphosphate oligoribonucleotides were unable to bind and activate RIG-I. Conversely, the addition of the synthetic complementary strand resulted in optimal binding and activation of RIG-I. Short double-strand conformation with base pairing of the nucleoside carrying the 5′ triphosphate was required. RIG-I activation was impaired by a 3′ overhang at the 5′ triphosphate end. These results define the structure of RNA for full RIG-I activation and explain how RIG-I detects negative-strand RNA viruses that lack long double-stranded RNA but do contain blunt short double-stranded 5′ triphosphate RNA in the panhandle region of their single-stranded genome. [Copyright &y& Elsevier]

Introduction. The incidence of early deep infection after arthroplasty of the knee is very low but could represent a serious future problem. Material and methods. The authors report on a 71-year-old woman with gonarthritis who was supplied with a total knee endoprosthesis and developed a local infection followed by septic shock. Results. The infection was evidently caused by a multiresistant Staphylococcus aureus (Staph. aureus). The primary clinical signs closely resembled a necrotizing fasciitis. Systemic and local application of vancomycin led to an improvement of the symptoms at secondary sites, but only the amputation of the primarily infected leg was lifesaving. Conclusion. In order to prevent such events, the authors recommend a number of additional presurgical measures. Firstly, a swab from the nose and throat should be taken prior to an elective surgery in patients with elevated risk of immunodeficiency, for example in patients with diabetes. The diabetes should be adequately treated before an elective operation is undertaken. Secondly, an early punction of the knee joint should be carried out if there is any doubt regarding inflammation. Isolated infectious agents should be grounds for early revision, which should always be completed with a rinsing procedure and with adequate antibiotics. Immunotherapy should be taken into consideration. Antiepidemic measures are recommended in cases with known Staph. aureus. [ABSTRACT FROM AUTHOR]

Background: Mortality of patients with a femoral neck fracture is high, especially within the first year after surgery, but also remains elevated thereafter. The aim of this study was to identify factors potentially associated with long-term mortality in patients homogeneously treated with hemiarthroplasty for femoral neck fracture. Methods: This retrospective cohort study was performed at a single level 1 national trauma center at the university hospital of Leipzig (Saxony, Germany). The study time-window was January 1, 2010 to December 31, 2020. Primary outcome measure was mortality depending on individual patient-related characteristics and perioperative risk factors. Inclusion criteria was a low-energy femoral neck fracture (Garden I-IV) in geriatric patients 60 years of age or older that were primarily treated with bipolar hemiarthroplasty. Date of death or actual residence of patients alive was obtained from the population register of the eastern German state of Saxony, Germany. The outcome was tested using the log-rank test and plotted using Kaplan-Meier curves. Unadjusted and adjusted for other risk factors such as sex and age, hazard ratios were calculated using Cox proportional hazards models and presented with 95% confidence intervals (CI). Results: The 458 included patients had a median age of 83 (IQR 77–89) years, 346 (75%) were female and 113 (25%) male patients. Mortality rates after 30 days, 1, 5 and 10 years were 13%, 25%, 60% and 80%, respectively. Multivariate regression analysis revealed age (HR = 1.1; p < 0.001), male gender (HR = 1.6; p < 0.001), ASA-Score 3–4 vs. 1–2 (HR = 1.3; p < 0.001), dementia (HR = 1.9; p < 0.001) and a history of malignancy (HR = 1.6; p = 0.002) as independent predictors for a higher long-term mortality risk. Perioperative factors such as preoperative waiting time, early surgical complications, or experience of the surgeon were not associated with a higher overall mortality. Conclusions: In the present study based on data from the population registry from Saxony, Germany the 10-year mortality of older patients above 60 years of age managed with hemiarthroplasty for femoral neck fracture was 80%. Independent risk factors for increased long-term mortality were higher patient age, male gender, severe comorbidity, a history of cancer and in particular dementia. Perioperative factors did not affect long-term mortality. [ABSTRACT FROM AUTHOR]

A PCR method based on the repetitive IS1245 sequence was evaluated for the detection of Mycobacterium avium bacteraemia in AIDS patients. Two blood preparation methods were applied: lysis of erythrocytes using a hypotonic buffer and Ficoll density centrifugation. Results were compared with culture and PCR amplification of the non-repetitive pMav22 sequence. Fifty-one of 251 tested samples grew M. avium. Bacterial densities lower than 10 cfu/ml blood were frequent, they occurred in 59% of blood samples from patients with mycobacteraemia. Inhibitory substances were detected more frequently with the lysis method (36%) than the Ficoll processed samples (19%). While specificity of PCR was high, sensitivities varied according to the methods used and the load of infection in the bloodstream. False-negative PCR results were attributable to low level bacteraemia and inhibition of PCR. Moreover, 1 of 186 and 9 of 51 M. avium strains investigated lacked the IS1245 and the pMav22 sequence, respectively. Sensitivities of culture, IS1245- and pMav22-based PCR were 88, 64 and 58% within the lysis processed samples and 95, 86 and 50% using Ficoll prepared samples, respectively. Thus, we conclude that IS1245-based PCR is a rapid and specific method for diagnosing M. avium bacteraemia and shows a higher sensitivity than single copy gene targets, but that the sensitivity is inferior to culture. [ABSTRACT FROM AUTHOR]

Process Analytical Technologies (PATs) are taking a key role in the run for automatization in the biopharmaceutical industry. Spectroscopic methods such as Raman spectroscopy or mid‐infrared (MIR) spectroscopy are getting more recognition in the recent years for inline monitoring of bioprocesses due to their ability to measure various molecules simultaneously. However, their dependency on laborious model calibration making them a challenge to implement. In this study, a novel one‐point calibration that requires a single reference point prior to the inline monitoring of glucose and lactate in bioprocesses with MIR spectroscopy is assessed with 22 mammalian cell perfusion (PER) processes in two different scales and four different products. Concentrations are predicted over all PERs runs with a root mean square error (RMSE) of 0.29 g/L for glucose and 0.24 g/L for lactate, respectively. For comparison conventional partial least square regression (PLSR) models were used and trained with spectroscopic data from six bioreactor runs in two different scales and three products. The general accuracy of those models (RMSE of 0.41 g/L for glucose and 0.16 g/L for lactate) are in the range of the accuracy of the one‐point calibration. This shows the potential of the one‐point calibration as an approach making spectroscopy more accessible for bioprocess development. [ABSTRACT FROM AUTHOR]

This prospective observational study had two aims: (I) to assess whether a preoperative dental screening before endoprosthesis (EP) implantation with need-based dental intervention would decrease the prevalence of periprosthetic joint infection (PJI) and (II) to evaluate whether instructed orthopedic surgeons would achieve similar results in oral screening as dentists. The preoperative oral health statuses of the patients, prior to EP insertion, were either evaluated by the patients' general dentists (Ia) or, if the patient had not visited a general dentist, by an instructed orthopedic surgeon (Ib). Both the dentist and orthopedic surgeon used standardized risk estimation (low risk, moderate risk, and high risk) for an oral-health-related infectious complication after EP insertion, including a recommendation for further management of the patient. If required, a need-based dental rehabilitation was performed. In addition, retrospective data evaluation of a comparison group (II) was performed, which had not been screened orally preoperatively. A total of 777 patients (screening group (I): n = 402, of which 229 were screened by a dentist (Ia), 173 were screened by an orthopedic surgeon (Ib); comparison group (II): n = 375) were included. No general association between early infection rate and preoperative oral screening in general was found (1% PJI in screening group (I), 1.6% PJI in comparison group (II); p = 0.455). However, screening performance (dentist vs. orthopedic surgeon) had a significant impact on the prevalence of developed PJIs (p = 0.021). Thereby, 100% of observed infections in the screening group (I) occurred in the group with previous oral screening by an orthopedic surgeon (Ib). Furthermore, the C-reactive protein (CRP) value at discharge was significantly lower when general preoperative oral screening had been performed (group I vs. group II, p = 0.03). Only preoperative oral screening by a dentist had the potential to reduce oral-focus-associated EP infections; therefore, increased attention should be paid to the further promotion of interdisciplinary work between dentists and orthopedic surgeons. Dental screenings, using objectifiable criteria, as applied in this study, seem reasonable but require further validation in larger cohorts. [ABSTRACT FROM AUTHOR]

Introduction: Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000–7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA). Materials and methods: The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8–1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA). Results: A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher—but not significant—mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible. Conclusions: The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the diagnostic value of simultaneous 18F-fluordeoxyglucose positron emission tomography/magnetic resonance imaging (PET/MRI) in suspected periprosthetic joint infection (PJI) of the hip and knee. Methods: Sixteen prostheses from 13 patients with suspected PJI were prospectively examined using PET/MRI. Image datasets were evaluated in consensus by a radiologist and a nuclear physician for the overall diagnosis of 'PJI' (yes/no) and its anatomical involvement, such as the periprosthetic bone margin, bone marrow, and soft tissue. The imaging results were compared with the reference standard obtained from surgical or biopsy specimens and subjected to statistical analysis. Results: Using the reference standard, ten out of the 13 prostheses (ten hips, threes knees) were diagnosed with PJI. Using PET/MRI, every patient with PJI was correctly diagnosed (sensitivity, 100%; specificity, 100%). Considering the anatomical regions, the sensitivity and specificity were 57% and 50% in the periprosthetic bone margin, 75% and 33% in the bone marrow, and 100% and 100% in the soft tissue. Conclusion: PET/MRI can be reliably used for the diagnosis of PJI. However, assessment of the periprosthetic bone remains difficult due to the presence of artefacts. Thus, currently, this modality is unlikely to be recommended in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this cross-sectional cohort study was to evaluate a comprehensive dental examination and referral concept for patients prior to endoprosthesis (EP) implantation in an interdisciplinary setting. Methods: Patients, who were prepared for EP surgery in the clinic for orthopaedics, were referred to the dental clinic for a dental examination. Thereby, dental and periodontal treatment need, radiographic and temporomandibular joint findings were assessed. Based on oral and radiographic investigation, a risk classification for potential source of prosthetic infection was performed. If potential oral foci of EP infection were present (e.g., apically radiolucent teeth, severe periodontitis or additional inflammatory findings), patients were classified as at high risk for EP infection with oral origin. Those individuals were allocated to their family dentist or special clinic for dental treatment prior to EP surgery. Results: A total of 311 patients were included (mean age: 67.84 ± 10.96 years, 51% male). A dental treatment need of 33% was found, while the periodontal treatment need was 83%. Thirty-one percent of patients showed at least one apical radiolucency (a sign of chronic infection/inflammation). Furthermore, additional findings such as radiographic signs of sinusitis maxillaris were found in 24% of patients. Temporomandibular disease was probable in 17% of individuals. One-third (34%) were assigned to the high risk group for an EP infection with oral origin. Conclusion: German patients before EP have a high periodontal treatment need and show frequently (34%) a potential oral focus of infection, underlining the necessity of including dental examination and risk stratification as part of the pre-operative assessment prior to EP implantation. Therefore, an approach as applied in this study appears reasonable for those individuals. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the application of Pictorial Representation of Illness and Self-Measure (PRISM) in educating patients regarding oral health before endoprosthesis (EP). Methods: The study consisted of two parts: (I) a cross-sectional study, where patients received a PRISM interview, oral health briefing and oral examinations (treatment need, oral focus). (II) In an observational part, patients were randomly assigned to either PRISM task (Test) or flyer-based verbal briefing (Control). Before and after the interviews, patients answered a questionnaire regarding importance of oral health for EP. Results: (I) 122 patients were included. The distance between subject ("myself") and objects (oral health issues or EP) in the PRISM task were mainly not associated with age, gender, and oral conditions. In part (II), 80 patients (PRISM: n = 40, Control: n = 40) were included. After the interview, the values for perceived relationship between EP and teeth (p < 0.01), EP and gums (p < 0.01), and EP and dental consultations (p < 0.01) significantly increased in both groups. Both groups perceived a high benefit of the interview and felt well educated. Conclusions: PRISM has comparable positive effects like a flyer-based verbal briefing. PRISM as a novel visual tool can support the patient education regarding oral health before EP. [ABSTRACT FROM AUTHOR]

A setup for the simultaneous measurement of mid-infrared spectra and static light scattering is de- scribed that can be used for the analysis of the formation of nanoscale and microscopic aggregates from smaller molecules to biopolymers. It can be easily integrated into sample chambers of infrared spectrometers or combined with laser beams from tunable infrared lasers. Here, its use for the analysis of the formation of amyloid fibrils from intact proteins is demonstrated. The formation of amyloid fibrils or plaques from proteins is a widespread and pathogenetic relevant process, and a number of diseases are caused and correlated with the deposition of amyloid fibrils in cells and tissues. The molecular mechanisms of these transformations, however, are still unclear. We report here the simultaneous measurement of infrared spectra and static light scattering for the analysis of fibril formation from egg-white lysozyme. The transformation of the native form into non-native forms rich in β-sheet structure is measured by analysis of the amide I spectral region in the infrared spectra, which is sensitive for local structures. At the same time, light scattering signals at forward direction as well as the forward/backward ratio, which are sensitive for the number of scattering centers and their approximate sizes, respectively, are collected for the analysis of fibril growth. Thermodynamic and kinetic parameters as well as mechanistic information are deduced from the combination of the two complementary techniques. [ABSTRACT FROM AUTHOR]

To investigate, whether hyperspectral imaging (HSI) is able to reliably differentiate between healthy and damaged cartilage tissue. A prospective diagnostic study was performed including 21 patients undergoing open knee surgery. HSI data were acquired during surgery, and the joint surface's cartilage was assessed according to the ICRS cartilage injury score. The HSI system records light spectra from 500 to 1000 nm and generates several parameters including tissue water index (TWI) and the absorbance at 960 nm and 540 nm. Receiver operating characteristic curves were calculated to assess test parameters for threshold values of HSI. Areas with a cartilage defect ICRS grade ≥ 3 showed a significantly lower TWI (p = 0.026) and higher values for 540 nm (p < 0.001). No difference was seen for 960 nm (p = 0.244). For a threshold of 540 nm > 0.74, a cartilage defect ICRS grade ≥ 3 could be detected with a sensitivity of 0.81 and a specificity of 0.81. TWI was not suitable for cartilage defect detection. HSI can provide reliable parameters to differentiate healthy and damaged cartilage. Our data clearly suggest that the difference in absorbance at 540 nm would be the best parameter to achieve accurate identification of damaged cartilage. [ABSTRACT FROM AUTHOR]

Background: Recombinant antibodies are essential reagents for research, diagnostics and therapy. The well established production host Escherichia coli relies on the secretion into the periplasmic space for antibody synthesis. Due to the outer membrane of Gram-negative bacteria, only a fraction of this material reaches the medium. Recently, the Gram-positive bacterium Bacillus megaterium was shown to efficiently secrete recombinant proteins into the growth medium. Here we evaluated B. megaterium for the recombinant production of antibody fragments. Results: The lysozyme specific single chain Fv (scFv) fragment D1.3 was succesfully produced using B. megaterium. The impact of culture medium composition, gene expression time and culture temperatures on the production of functional scFv protein was systematically analyzed. A production and secretion at 41°C for 24 h using TB medium was optimal for this individual scFv. Interestingly, these parameters were very different to the optimal conditions for the expression of other proteins in B. megaterium. Per L culture supernatant, more than 400 μg of recombinant His6-tagged antibody fragment were purified by one step affinity chromatography. The material produced by B. megaterium showed an increased specific activity compared to material produced in E. coli. Conclusion: High yields of functional scFv antibody fragments can be produced and secreted into the culture medium by B. megaterium, making this production system a reasonable alternative to E. coli. [ABSTRACT FROM AUTHOR]

Background: Improved oncological and surgical measures now enable curative treatment of malignant lower extremity tumors in majority of cases. Complication rates associated with surgical resection of lower extremity tumors and replacement with megaendoprostheses are high. The aim of this study was to identify risk factors that predispose to revision surgery following the use of megaimplants in curative treatment of malignant tumors of the lower extremities. Methods: this retrospective study included patients aged ≥ 18 years who underwent implantation of a megaendoprosthesis for tumors or metastatic lesions of the lower extremities between January 2010 and December 2020. Baseline characteristics and information on adjuvant treatment, hospitalization time, comorbidities, mobility, complications, and revision surgery were considered. Primary outcomes were revision surgery and reasons for revision. Secondary outcomes were in-hospital complications and the duration of hospitalization. Results: Fifty-four patients (48% female, age 63 years, SD 15) were available for final analysis. Surgeries were performed at hip level in 37 patients (68.5%) and at knee level in 17 patients (31.5%). Revision for wound-related causes was performed in 12 cases (22.2%), with microbiological proof of infection in 8 cases (14.8%). Revision for hip joint instability was carried out in 4 cases (7.4%) and for disconnection between components of the megaimplant in 2 cases (3.7%). Those patients requiring a wound-related revision had undergone a longer primary surgical intervention than those who required an implant-related revision (276 vs 134 min, p =.002). Wound drains after the primary implantation remained longer in situ in patients who later required revision surgery for wound-related complications (5 vs 3 days, p =.020). An ASA > 3 was associated with an increased likelihood for in-hospital complications in general (p =.041), and in-hospital death in particular (p =.012). Conclusions: The management of malignant tumors of the lower extremities with megaendoprostheses is associated with a high rate of wound-related complications. Swift surgical performance and early postoperative removal of wound drains minimize the risk of complications in general and the necessity of revision surgery in particular. Patients with more comorbidities were more likely to suffer in-hospital complications. [ABSTRACT FROM AUTHOR]

Background: Molecular identification of Mycobacterium species has two primary advantages when compared to phenotypic identification: rapid turn-around time and improved accuracy. The information content of the 5' end of the 16S ribosomal RNA gene (16S rDNA) is sufficient for identification of most bacterial species. However, reliable sequence-based identification is hampered by many faulty and some missing sequence entries in publicly accessible databases. Methods: In order to establish an improved 16S rDNA sequence database for the identification of clinical and environmental isolates, we sequenced both strands of the 5' end of 16S rDNA (Escherichia coli positions 54 to 510) from 199 mycobacterial culture collection isolates. All validly described species (n = 89; up to March 21, 2000) and nearly all published sequevar variants were included. If the 16S rDNA sequences were not discriminatory, the internal transcribed spacer (ITS) region sequences (n = 84) were also determined. Results: Using 5'-16S rDNA sequencing a total of 64 different mycobacterial species (71.9%) could be identified. With the additional input of the ITS sequence, a further 16 species or subspecies could be differentiated. Only Mycobacterium tuberculosis complex species, M. marinum / M. ulcerans and the M. avium subspecies could not be differentiated using 5'-16S rDNA or ITS sequencing. A total of 77 culture collection strain sequences, exhibiting an overlap of at least 80% and identical by strain number to the isolates used in this study, were found in the GenBank. Comparing these with our sequences revealed that an average of 4.31 nucleotide differences (SD ± 0.57) were present. Conclusions: The data from this analysis show that it is possible to differentiate most mycobacterial species by sequence analysis of partial 16S rDNA. The high-quality sequences reported here, together with ancillary information (e.g., taxonomic, medical), are available in a public database, which is currently being expanded in the RIDOM project http://www.ridom-rdna.de), for similarity searches. [ABSTRACT FROM AUTHOR]

Endoprosthetic surgery can lead to relevant blood loss resulting in red blood cell (RBC) transfusions. This study aimed to identify risk factors for blood loss and RBC transfusion that enable the prediction of an individualized transfusion probability to guide preoperative RBC provision and blood saving programs. A retrospective analysis of patients who underwent primary hip or knee arthroplasty was performed. Risk factors for blood loss and transfusions were identified and transfusion probabilities computed. The number needed to treat (NNT) of a potential correction of preoperative anemia with iron substitution for the prevention of RBC transfusion was calculated. A total of 308 patients were included, of whom 12 (3.9%) received RBC transfusions. Factors influencing the maximum hemoglobin drop were the use of drain, tranexamic acid, duration of surgery, anticoagulation, BMI, ASA status and mechanical heart valves. In multivariate analysis, the use of a drain, low preoperative Hb and mechanical heart valves were predictors for RBC transfusions. The transfusion probability of patients with a hemoglobin of 9.0–10.0 g/dL, 10.0–11.0 g/dL, 11.0–12.0 g/dL and 12.0–13.0 g/dL was 100%, 33.3%, 10% and 5.6%, and the NNT 1.5, 4.3, 22.7 and 17.3, while it was 100%, 50%, 25% and 14.3% with a NNT of 2.0, 4.0, 9.3 and 7.0 in patients with a drain, respectively. Preoperative anemia and the insertion of drains are more predictive for RBC transfusions than the use of tranexamic acid. Based on this, a personalized transfusion probability can be computed, that may help to identify patients who could benefit from blood saving programs. [ABSTRACT FROM AUTHOR]

Background: The design and internal layout of modern operating rooms (OR) are influencing the surgical team's collaboration and communication, ergonomics, as well as intraoperative hygiene substantially. Yet, there is no objective method for the assessment and design of operating room setups for different surgical disciplines and intervention types available. The aim of this work is to establish an improved OR setup for common procedures in arthroplasty.Methods: With the help of computer simulation, a method for the design and assessment of enhanced OR setups was developed. New OR setups were designed, analyzed in a computer simulation environment and evaluated in the actual intraoperative setting. Thereby, a 3D graphical simulation representation enabled the strong involvement of clinical stakeholders in all phases of the design and decision-making process of the new setup alternatives.Results: The implementation of improved OR setups reduces the instrument handover time between the surgeon and the scrub nurse, the travel paths of the OR team as well as shortens the procedure duration. Additionally, the ergonomics of the OR staff were improved.Conclusion: The developed simulation method was evaluated in the actual intraoperative setting and proved its benefit for the design and optimization of OR setups for different surgical intervention types. As a clinical result, enhanced setups for total knee arthroplasty and total hip arthroplasty surgeries were established in daily clinical routine and the OR efficiency was improved. [ABSTRACT FROM AUTHOR]

Bone diseases represent an increasing health burden worldwide, and basic research remains necessary to better understand the complexity of these pathologies and to improve and expand existing prevention and treatment approaches. In the present study, 216 bone samples from the caput femoris and collum femoris of 108 patients with degenerative or dysplastic coxarthrosis, hip fracture, or osteonecrosis were evaluated for the proportion of trabecular bone (TB) and expression of parathyroid hormone (PTH) type 1 receptor (PTH1R), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Serum levels of PTH, OPG, soluble RANKL (sRANKL), alkaline phosphatase (AP), osteocalcin, total procollagen type-1 intact N-terminal propeptide (TP1NP), tartrate-resistant acid phosphatase type 5b (TRAP5b), sclerostin, and C-telopeptide of type-1 collagen (ICTP) were also determined. Age was positively correlated with serum levels of PTH, OPG, and sclerostin but negatively associated with TB and sRANKL. Women exhibited less TB, lower sclerostin and ICTP, and higher TRAP5b. Impaired kidney function was associated with shorter bone decalcification time, less TB, lower sRANKL, and higher serum PTH, OPG, and sclerostin. Furthermore, correlations were observed between bone PTH1R and OPG expression and between serum PTH, OPG, and AP. There were also positive correlations between serum OPG and TP1NP; serum OPG and sclerostin; serum AP, osteocalcin, and TRAP5b; and serum sclerostin and ICTP. Serum OPG was negatively associated with sRANKL. In summary, clear relationships between specific bone metabolism markers were observed, and distinct influences of age, sex, and kidney function, thus underscoring their suitability as diagnostic or prognostic markers. [ABSTRACT FROM AUTHOR]

The present paper is concerned with the investigation of the phenomenon of long-term bone remodelling on cementless hip replacements. Changes in bone density in the periprosthetic region around the stem, measured by dual X–ray absorptiometry (DXA), were used as a measure of the osseous adaptation reaction. A postoperative follow-up of the use of four different types of prostheses of varying design after on average 13.3 (11.4–14.5) years. Specifically, the prostheses assessed in this study were the CLS/Spotorno stem with the Allofit cup by Zimmer, the Vision 2000 stem with the Duraloc cup by DePuy Synthes, the AlphaFit stem with the AlphaLock cup by Corin and the Mayo stem with the Trilogy cup by Zimmer. For the DXA measurement, the femur was divided into the zones suggested by Gruen et al. On the femur, there was a significant reduction in bone mineral density (BMD) in the proximal Region Of Interest (ROI) 1 (p = 0.003) and 7 (p < 0.001), whilst there was a significant increase in ROI 4 (p = 0.03). A greater degree of bone atrophy was seen in patients aged 60 years and older and in female patients. A remarkable finding when comparing the stems was a significantly greater reduction in BMD in ROI 6 (p = 0.003) in the case of the Vision 2000 stem and a markedly, but not statistically significantly smaller reduction in BMD in ROI 7 (p = 0.18) in the case of the short-stem Mayo-type prosthesis. The best clinical results were found with the use of the latter. The investigations provide a starting point for establishing a differential indication in the choice of prosthesis types, depending on age and sex, the use of short-stem prostheses, as well as the administration of bone-effective drugs for the prevention of stress shielding. [ABSTRACT FROM AUTHOR]

Atraumatic femoral head necrosis is a rare pathological change of the femoral head. It is characterized by local necrosis of the cancellous bone as a result of reduced blood supply to the bone. Even today it remains unclear how to assess the hardness of the necrosis, whether it is soft tissue that is easily removed, or hard tissue that is difficult to resect. Femoral heads with primary coxarthrosis were selected as a comparison group. For this purpose, 49 femoral heads obtained during total hip arthroplasty surgery with either condition (23 femoral head necrosis, 26 coxarthrosis) were transferred to the testing laboratory in fresh condition. Cylindrical specimens were obtained using a tenon cutter along the main trabecular load direction in the subchondral region of the femoral head. Additionally, thin bone slices were extracted proximal and distal to the specimens for density measurements. Brass plates were glued to the circular surfaces of the specimens. After curing of the adhesive, the specimens were mounted in the testing machine and destructive uniaxial compression tests were conducted. The recorded mean compressive strengths and elastic moduli were almost identical for both groups, but the necrosis group showed significantly higher data scattering and range regarding the elastic modulus. The mean density of the coxarthrosis specimens was significantly higher than that of the necrotic specimens. The mechanical properties of cancellous bone vary considerably in the presence of femoral head necrosis. The existence of hard necrosis implies a potential challenge regarding the clinical resection of these tissues. • Femoral head necrosis is very heterogeneous in appearance and mechanical properties. • Presence of sclerotic tissue has an increasing influence on the elastic modulus. • Mean density differs significantly between coxarthrosis and femoral head necrosis. [ABSTRACT FROM AUTHOR]

Background: The treatment aims of periprosthetic fractures (PPF) of the distal femur are a gentle stabilization, an early load-bearing capacity and a rapid postoperative mobilization of the affected patients. For the therapy planning of PPF a standardized classification is necessary which leads to a clear and safe therapy recommendation. Despite different established classifications, there is none that includes the types of prosthesis used in the assessment. For this purpose, the objective of this work is to create a new more extensive fracture and implant-related classification of periprosthetic fractures of the distal femur based on available classifications which allows distinct therapeutic recommendations.Methods: In a retrospective analysis all patients who were treated in the University Hospital Leipzig from 2010 to 2016 due to a distal femur fracture with total knee arthroplasty (TKA) were established. To create an implant-associated classification the cases were discussed in a panel of experienced orthopaedists and well-practiced traumatologists with a great knowledge in the field of endoprosthetics and fracture care. In this context, two experienced surgeons classified 55 consecutive fractures according to Su et al., Lewis and Rorabeck and by the new created classification. In this regard, the interobserver reliability was determined for two independent raters in terms of Cohen Kappa.Results: On the basis of the most widely recognized classifications of Su et al. as well as Lewis and Rorabeck, we established an implant-dependent classification for PPF of the distal femur. In accordance with the two stated classifications four fracture types were created and defined. Moreover, the four most frequent prosthesis types were integrated. Finally, a new classification with 16 subtypes was generated based on four types of fracture and four types of prosthesis. Considering all cases the presented implant-associated classification (κ = 0.74) showed a considerably higher interobserver reliability compared to the other classifications of Su et al. (κ = 0.39) as well as Lewis and Rorabeck (κ = 0.31). Excluding the cases which were only assessable by the new classification, it still shows a higher interobserver reliability (κ = 0.70) than the other ones (κ = 0.63 or κ = 0.45).Conclusions: The new classification system for PPF of the distal femur following TKA considers fracture location and implant type. It is easy to use, shows agood interobserver reliability and allows conclusions to be drawn on treatment recommendations. Moreover, further studies on the evaluation of the classification are necessary and planned. [ABSTRACT FROM AUTHOR]

Background: Hip and knee replacements in patients with bone defects after infection correlates with high rates of reinfection. In this vulnerable patient population, the prevention of reinfection is to be considered superordinate to the functionality and defect bridging. The use of silver coating of aseptic implants as an infection prophylaxis is already proven; however, the significance of these coatings in septic reimplantation of large implants is still not sufficiently investigated.Methods: In a retrospective analysis, 34 patients who have been treated with a modular mega-endoprosthesis after a cured bone infection of the lower limb (femur or tibia) have been evaluated. One group with 14 patients (NSCG: non silver- coated group) was supplied with the non silver- coated implants: MML München- Lübeck™ modular endoprosthesis system (AQ Implants, Ahrensburg, Germany) or MUTARS® Modular Universal Tumor And Revision System (Implantcast GmbH, Buxtehude, Germany). The other group with 20 patients (SCG: silver- coated group) was supplied with the silver- coated system of MUTARS®. In addition to the clinical findings and the patients' histories, specifically the reinfection rates, the patients' mobility was assessed using the New Mobility Score (NMS, by Parker and Palmer).Results: The median follow-up period was 72 months, ranging from 6 to 267 months. The dropout rate was 5.8%. The reinfection rate after healed reinfection in SCG was 40% (8/20), in NSCG 57% (8/14), p = 0.34; α =0.05. The time for reinfection was, on average, 14 months (1-72 months) in SCG and 8 months (1-48 months) in the NSCG (p = 0.61; α =0.05). The two groups showed no differences in the NMS.Conclusion: With this retrospective analysis, it can be determined that the rate of reinfection of modular mega-endoprostheses on the hip and knee joint after healed periprosthetic joint infection (PJI) can be reduced by the use of silver coated implants. The time until reinfection can also be delayed by utilizing silver coated implants. Due to the low number of cases of this highly specific patient population, no statistical significance could be determined. A positive effect, however, can be assumed through the use of silver coatings in mega-endoprostheses after an infectious situation. [ABSTRACT FROM AUTHOR]

Background: In spite of the improvement of many aspects around Total knee arthroplasty (TKA), there is still a group of 10% to 34% of patients who is not satisfied with the outcome. The therapy of chronic pain after TKA remains a medical challenge that requires an interdisciplinary therapy concept. The aim of this prospective pilot study was to evaluate the efficacy of a multimodal pain therapy in chronic complaints after TKA. Methods: In a prospective cohort pilot study, we included patients with chronic pain after TKA who obtained in-patient care, especially multimodal pain therapy (MMPT), for at least 10 days. Essential elements of this therapy concept were physiotherapy, pain medication therapy, topical application of ketamine, local infiltration and Traditional Chinese Medicine. Patients with varying causes of complaints were excluded in advance. Before the start of the study all test persons were informed and gave their written consent. Moreover, each patient was examined and questioned at hospital admission, discharge and at its first as well as second follow-up. Additionally, knee joint mobility and stability were investigated at all examination times. Results: From 03/07/2016 to 07/14/2016, 21 patients were included in the pilot study. 52% of the considered population were female (11 persons). The median age was 65 years (45-79 years) and the median stay in hospital amounted 9 days (8-14 days). The first follow-up was scheduled after six weeks (median: 38 days, 30-112 days) and the second one after six months (median: 8 months, 7-12 months). The number of patients of the first follow-up was 17 out of 21 (19% drop out). The drop out of the last follow-up accounted for 33%. All patients benefit from the presented applications and therapies with regard to pain, function and range of motion. Especially, during the period of in-patient treatment, nearly all patients have improved in all terms. However, during the first follow-up clear deteriorations occurred in all areas, which stagnated up to the second follow-up. The range of motion has even worsened slightly. Conclusions: With the presented pilot study on multimodal in-patient therapy of chronic complaints due to TKA, the improvement of pain, function and mobility could be verified, especially during the stationary stay. Even though the results deteriorate during the follow-up period, they did never relapse to their initial level. In order to ensure an effective treatment, a clear diagnostic algorithm is essential, by which treatable causes, such as low-grade infections or loosenings, are safely excluded. Further prospective studies are necessary to obtain precise statements on prospects of success of our therapy plan. [ABSTRACT FROM AUTHOR]

Correction to: Archives of Orthopaedic and Trauma Surgery https://doi.org/10.1007/s00402-021-... The original version of this article unfortunately contained a mistake. The correct given name and family name should be: Alexander Hofmann - Benjamin Fischer - Stefan Schleifenbaum - Sascha Kurz - Melanie Edel - Gudrun Borte - Gabriele Lehmann - Andreas Roth The original article has been corrected. [Extracted from the article]

Background: Modular mega-endoprosthesis systems are used to bridge very large bone defects and have become a widespread method in orthopaedic surgery for the treatment of tumours and revision arthroplasty. However, the indications for the use of modular mega-endoprostheses must be carefully considered. Implanting modular endoprostheses requires major, complication-prone surgery in which the limited salvage procedures should always be borne in mind. The management of periprosthetic infection is particularly difficult and beset with problems. Given this, the present study was designed to gauge the significance of periprosthetic infections in connection with modular mega-implants in the lower extremities among our own patients. Methods: Patients who had been fitted with modular endoprosthesis on a lower extremity at our department between September 1994 and December 2011 were examined retrospectively. A total of 101 patients with 114 modular prostheses were identified. Comprising 30 men (29.7 %) and 71 women (70.3 %), their average age at the time of surgery was 67 years (18-92 years). Results: The average follow-up period was 27 months (5 months and 2 weeks to 14 years and 11 months) and the drop-out rate was about 8.8 %. Altogether, there were 19 (17.7 %) endoprosthesis infections: 3 early infections and 16 late or delayed infections. The pathogen spectrum was dominated by coagulase-negative staphylococci (36 %) and Staphylococcus aureus (16 %), including 26 % multi-resistant pathogens. Reinfection occurred in 37 % of cases of infection. Tumours were followed by significantly fewer infections than the other indications. Infections were twice as likely to occur after previous surgery. Conclusion: In our findings modular endoprostheses (18 %) are much more susceptible to infection than primary endoprostheses (0.5-2,5 %). Infection is the most common complication alongside the dislocation of proximal femur endoprostheses. Consistent, radical surgery is essential - although even with an adequate treatment strategy, the recurrence rate is very high. Unfortunately, the functional results are frequently unsatisfactory, with amputation often being the last resort. Therefore, the indication for implantation must be carefully considered and discussed in great detail, especially in the case of multimorbid patients with previous joint infections. [ABSTRACT FROM AUTHOR]

Background: Recent research has focused on identifying chemical modulators of osteogenesis. We present initial findings on the osteoinductive properties of prostaglandin Е1 (Vasaprostan), using a rabbit model.Methods: Data were collected on callus formation in 14 male rabbits. These were divided into two groups (control and treatment) with 7 animals in each group. In all animals, the right tibia was fractured using a standardized protocol and stabilized by an intramedullary nail. Treatment group received a 5 μg/kg subcutaneous injection of PGE1/day during 10 postoperative days. Visual and radiological evaluation of callus formation was prospectively collected. After 30 days, all animals were killed and the tibia specimens were examined histologically.Results: In all the treatment group animals, fractures were consolidated radiologically by day 30. No treatment group animals and two control group animals were excluded form the experiment. In the control group, 4 animals demonstrated slower callus formation than the main group. Two control group animals were excluded from the experiment on the 20th day due to wound infection; one developed a nonunion. The mean coefficient of bone callus thickening in the main group was 2.08 (±0, 16) and 1.77 (±0.05) (p < 0.05) in the control group. Calculation of mean quantity of neogenic vessels in 10 random visual fields of the bone callus revealed 78 (±9.82) in the main group and 40 (±4.68) in the control group (p < 0.05).Conclusions: Our study demonstrates an increased rate and amount of bone callus formation in the group treated with prostaglandin E1 compared to the control group. Prospective radiological analysis was corroborated by histologic evaluation. [ABSTRACT FROM AUTHOR]

Summary The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5′-triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5′-triphosphorylated, backbone modifications and the 5′-ppp-linked methylguanosine ( m7 G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5′-terminal nucleotide (N 1 ) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N 1 -2′O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N 1 -2′O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N 1 -2′O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2′O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N 1 -2′O-methylation in RIG-I tolerance of self-RNA. [ABSTRACT FROM AUTHOR]

Background: Elective knee and hip arthroplasty is followed by infections in currently about 0.5-2.0 % of cases - a figure which is on the increase due to the rise in primary implants. Correct diagnosis early on is essential so that appropriate therapy can be administered. This work presents a retrospective analysis of the diagnoses of patients suffering infections after total hip or knee arthroplasty. Methods: 320 patients with prosthetic joint infection (PJI) following knee or hip arthroplasty were identified. They comprised a) 172 patients with an infection after total hip arthroplasty (THA): 56 % females (n = 96) and 44 % males (n = 76) with a mean age of 70.9 (39-92) years; and 148 patients with an infection after total knee arthroplasty (TKA): 55 % females (n = 82) and 45 % males (n = 66) with a mean age of 70.7 (15-87) years. Results: Although significantly more TKA than THA patients reported pain, erythema, a burning sensation and swelling, no differences between the two groups were observed with respect to dysfunction, fever or fatigue. However, significant differences were noted in the diagnosis of loosening (THA 55 %, TKA 31 %, p < 0.001) and suspected infection using conventional X-rays (THA 61 %, TKA 29 %, p < 0.001). FDG-PET-CT produced very good results in nearly 95 % of cases. There were no differences between THA and TKA patients regarding levels of inflammation markers. Histological evaluation proved to be significantly better than microbiological analysis. Summary: The clinical picture may be non-specific and not show typical inflammatory symptoms for a long time, particularly in PJI of the hip. As imaging only provides reliable conclusions after the symptoms have persisted for a long time, morphological imaging is not suitable for the detection of early infections. FDG-PT-CT proved to be the most successful technique and is likely to be used more frequently in future. Nevertheless, there are currently no laboratory parameters which are suitable for the reliable primary diagnosis of PJI. Diagnosis requires arthrocentesis, and the fluid obtained should always be examined both microbiologically and histologically. [ABSTRACT FROM AUTHOR]

Purpose: The cementless implantation of hip replacement cups may be performed with and without the additional use of acetabular screws. If the surgeon uses screws or not depends on variable factors. In general, the use of screws is intended to increase the primary stability of the cup. Whether screws increase the initial stability of the cup construct, or even reduce it in part, is the subject of considerable debate in the literature. It is also unclear whether the additional screws lead to increased wear or increased periacetabular osteolysis over the long-term course.Methods: Two hundred eleven patients from a previous study with a minimum follow-up of 10.7 years were included. Of these, 68 patients with 82 total hip arthroplasties (THA) were given clinical and radiological follow-up examinations. Of these, 52 had been fitted without screws and 30 with screws. On the basis of radiographs, annual wear and osteolysis were quantified. The clinical results were recorded by means of VAS, HHS, and WOMAC scores.Results: Significantly more periacetabular osteolysis was found if additive acetabular screws had been used. No difference was found in relation to the volumetric wear per year. Likewise, no difference was found with regard to the clinical scores.Conclusions: The use of additive acetabular screws leads to increased osteolysis in the periacetabular bone stock. Insofar as the primary stability of the cementless cup construct allows it, no additional acetabular screws should be used. [ABSTRACT FROM AUTHOR]

Recent theory predicted that the quantum spin Hall effect, a fundamentally new quantum state of matter that exists at zero external magnetic field, may be realized in HgTe/(Hg,Cd)Te quantum wells. We fabricated such sample structures with low density and high mobility in which we could tune, through an external gate voltage, the carrier conduction from n-type to p-type, passing through an insulating regime. For thin quantum wells with well width d < 6.3 nanometers, the insulating regime showed the conventional behavior of vanishingly small conductance at Low temperature. However, for thicker quantum wells (d > 6.3 nanometers), the nominally insulating regime showed a plateau of residual conductance close to 2e2lh, where e is the electron charge and h is Planck's constant. The residual conductance was independent of the sample width, indicating that it is caused by edge states. Furthermore, the residual conductance was destroyed by a small external magnetic field. The quantum phase transition at the critical thickness, d = 6.3 nanometers, was also independently determined from the magnetic field-induced insulator-to-metal transition. These observations provide experimental evidence of the quantum spin Hall effect. [ABSTRACT FROM AUTHOR]

Emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis isolates constitutes a threat to public health worldwide. This study aimed at acquiring first epidemiological data for Guyana. Thirty-six M. tuberculosis isolates from patients of the Georgetown Chest Clinic were subjected to susceptibility testing on solid agar and in broth media. Resistance to at least one first-line drug was observed in 8 (22.2%, 95% confidence interval 8.3–36.1%) and simultaneous resistance to rifampicin and isoniazid (MDR) in 4 (11.1%, 95% confidence interval 0.6–21.6%) of the 36 isolates. The risk of infection with resistant isolates was significantly related to earlier antituberculosis therapy ( P = 0.040). These data indicate a high proportion of resistant M. tuberculosis isolates in Guyana and call for the implementation of control strategies based on an improved laboratory diagnosis of TB. [ABSTRACT FROM AUTHOR]

KeY is a tool that provides facilities for formal specification and verification of programs within a commercial platform for UML based software development. Using the KeY tool, formal methods and object-oriented development techniques are applied in an integrated manner. Formal specification is performed using the Object Constraint Language (OCL), which is part of the UML standard. KeY provides support for the authoring and formal analysis of OCL constraints. The target language of KeY based development isJava Card DL, a proper subset ofJavafor smart card applications and embedded systems. KeY uses a dynamic logic forJava Card DLto express proof obligations, and provides a state-of-the-art theorem prover for interactive and automated verification. Apart from its integration into UML based software development, a characteristic feature of KeY is that formal specification and verification can be introduced incrementally. [ABSTRACT FROM AUTHOR]

Presents a case study of Lassa fever virus found in cerebrospinal fluid of a Nigerian patient. Clinical manifestations of the disease; Diagnostic and laboratory procedure adopted and its results; Treatment approaches.

The femoral head is of central importance for the force transmission from the suprapelvic body mass to the lower extremity. However, the condition of the subcortical bone and its mechanical properties in case of pathological changes due to coxarthrosis or femoral head necrosis differ from the healthy condition. Fresh femoral heads were gathered during hip total endoprosthesis surgeries and cylindrical cancellous bone samples were extracted with a hollow drill. By means of a uniaxial tensile-compression test system, the compressive strength was determined for two different specimen types (fresh and 24 h storage in acetone). Exemplary tests on an exceptionally large femoral head were performed to compare properties of fresh, fresh-deep-frozen and acetone-stored samples. The deformation behaviour and the material parameters determined were very heterogeneous. For most of the specimens, a destructive material test was successfully carried out, i.e. the compressive strength was determined. The average strength of fresh specimens was slightly higher than that of acetone specimens. On the other hand, the average Young's modulus of the acetone specimens was higher than that of the fresh specimens. The lower Young's moodulus of the fresh samples compared to the acetone samples could indicate a causal effect of the degreasing influence of the acetone. The partly considerable individual differences in compressive strength and failure compression can have patient-specific influencing factors such as constitution and physical fitness as well as causes in the initial pathological condition. • Acetone decreases the compressive strength of cancellous bone. • Acetone significantly increases the modulus of elasticity of cancellous bone. • Cancellous bone structure, pore sizes and elasticity show great individual differences. [ABSTRACT FROM AUTHOR]

For the generation of representative volume elements a statistical description of the relevant parameters is necessary. These parameters usually describe the geometric structure of a single grain. Commonly, parameters like area, aspect ratio, and slope of the grain axis relative to the rolling direction are applied. However, usually simple distribution functions like log normal or gamma distribution are used. Yet, these do not take the interdependencies between the microstructural parameters into account. To fully describe any metallic microstructure though, these interdependencies between the singular parameters need to be accounted for. To accomplish this representation, a machine learning approach was applied in this study. By implementing a Wasserstein generative adversarial network, the distribution, as well as the interdependencies could accurately be described. A validation scheme was applied to verify the excellent match between microstructure input data and synthetically generated output data. [ABSTRACT FROM AUTHOR]

• Tailored optimization methods for interacting particle systems in the mean-field limit. • Derivation of the adjoint equation for a nonlocal Vlasov equation. • The " first optimize, then discretize " approach allows for performant discretizations of the forward and adjoint equations. • Numerical solution of a large scale optimization problem with 4D phase space. • Numerical verification of the mean-field limit in optimization problems. Controlling large particle systems in collective dynamics by a few agents is a subject of high practical importance, e.g., in evacuation dynamics. In this paper we study an instantaneous control approach to steer an interacting particle system into a certain spatial region by repulsive forces from a few external agents, which might be interpreted as shepherd dogs leading sheep to their home. We introduce an appropriate mathematical model and the corresponding optimization problem. In particular, we are interested in the interaction of numerous particles, which can be approximated by a mean-field equation. Due to the high-dimensional phase space this will require a tailored optimization strategy. The arising control problems are solved using adjoint information to compute the descent directions. Numerical results on the microscopic and the macroscopic level indicate the convergence of optimal controls and optimal states in the mean-field limit, i.e., for an increasing number of particles. [ABSTRACT FROM AUTHOR]