Front propagation steered by a high-wavenumber modulation: Theory and experiments.

Homogeneously driven dynamical systems exhibit multistability. Depending on the initial conditions, fronts present a rich dynamical behavior between equilibria. Qualitatively, this phenomenology is persistent under spatially modulated forcing. However, the understanding of equilibria and front dynamics organization is not fully established. Here, we investigate these phenomena in the high-wavenumber limit. Based on a model that describes the reorientation transition of a liquid crystal light valve with spatially modulated optical forcing and the homogenization method, equilibria and fronts as a function of forcing parameters are studied. The forcing induces patterns coexisting with the uniform state in regions where the system without forcing is monostable. The front dynamics is characterized theoretically and numerically. Experimental results verify these phenomena and the law describing bistability, showing quite good agreement.

[Deployment of the in-hospital emergency team in a tertiary care university hospital : Data analysis for the time period 2013-2016 in North-Rhine/Westphalia]. / Einsätze des innerklinischen Notfallteams eines überregionalen Maximalversorgers : Datenanalyse für den Zeitraum 2013­2016 im nordrhein-westfälischen Raum.

BACKGROUND: Recent studies demonstrated that in-hospital emergencies are linked to a higher patient mortality. In approximately 10% of patients an unexpected incident occurs during the hospital stay. Therefore, the establishment of in-hospital medical emergency teams (MET) is becoming more important in the interdisciplinary emergency treatment. The aim of this study was an analysis of medical documentation, operational tactics and procedures taken by MET of the University Hospital of Cologne in a 4-year period ranging from 2013 to 2016. MATERIAL AND METHODS: A retrospective analysis of 1664 emergency forms from MET activities at the University Hospital of Cologne from 1 January 2013 to 31 December 2016 was carried out. Every MET activation call via the emergency telephone number (5555) and subsequent emergency treatment was recorded using a standardized documentation form. The registry number on ClinicalTrials.gov is NCT03786445. RESULTS: There were 1664 emergency team calls in the whole study period. Between 2013 (404 calls) and 2016 (461 calls) the number of calls increased by 11.4%. The total mission time of the MET increased in the study period from 8342 min (2013) to 10,800 min (2016, +29.5%) and the average mission time increased from 2013 (35 min) to 2016 (40 min) by 14.3%. The primary reason for activation was collapse or syncope and was the underlying cause for 29% of calls. The number of deployments for emergencies at weekends was 50% of those during weekdays and 6.5% of the calls were for cardiopulmonary resuscitation (CPR). CONCLUSION: Analysis of data revealed that the number of MET calls, total operating time and average deployment time increased from 2013 to 2016. The primary reason for MET activations was collapse or syncope and every 17th deployment was for cardiopulmonary resuscitation. The incidence of in-hospital cardiac arrests decreased during the study period.

Individual cow's milk allergens as prognostic markers for tolerance development?

BACKGROUND: Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful. OBJECTIVE: In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time. METHODS: A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM. RESULTS: The individual likelihood of outgrowing CMA significantly correlates with a low level of CM-specific IgE as well as a low level of specific IgE to α-lactalbumin, ß-lactoglobulin (Bos d5.0102), κ-casein and α(s1) -casein. No significant correlation was found for IgE levels to total casein, lactoferrin, ß-casein and ß-lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α-lactalbumin, ß-lactoglobulin and total casein. CONCLUSIONS: CM-specific IgE is a good prognostic marker for persistence of CMA. In addition, component-resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.

Bacterial porins: structure and function.

Within the class of integral membrane proteins, the bacterial porins display a remarkable resistance to denaturants and proteases. This stability is probably crucial for the formation of highly ordered, three-dimensional crystals. Structural analysis of these crystals has been possible in atomic detail. This analysis has revealed interesting features, such as the aromatic girdles, and has helped to explain several observations, including the porins' ability to discriminate between polar and non-polar solutes. Recent research has thus improved our understanding of the porins in a qualitative fashion.

[Enhanced Recovery After Surgery (ERAS®) after radical cystectomy-current data]. / Aktuelle Studienlage der Enhanced Recovery After Surgery (ERAS®) nach radikaler Zystektomie.

BACKGROUND: Radical cystectomy is associated with considerable morbidity and mortality. Based on the solid evidence in colorectal surgery, fast-track/ERAS® (Enhanced Recovery After Surgery) protocols have been developed to improve the perioperative management of patients undergoing radical cystectomy. OBJECTIVES: To review the literature and guidelines and evaluate the evidence regarding the different components of ERAS® protocols. MATERIALS AND METHODS: Systemic literature search and evaluation of relevant guidelines. RESULTS: The majority of ERAS® recommendations for radical cystectomy are based on extrapolations of abdominal surgery studies. Four randomized, controlled trials and one ERAS® guideline were published for radical cystectomy. ERAS® seems to shorten length of stay without increasing the complication rate. Key elements are no bowel preparation, no nasogastric tube, optimized fluid substitution, multimodal pain management, early mobilization, and oral diet. CONCLUSIONS: Implementation of ERAS® requires multidisciplinary collaboration. Individualization of an ERAS® program, identification of the most important components and adaption to the specific needs of radical cystectomy patients are future goals.

Localized standing waves induced by spatiotemporal forcing.

Particle-type solutions are observed in out-of-equilibrium systems. These states can be motionless, oscillatory, or propagative depending on the injection and dissipation of energy. We investigate a family of localized standing waves based on a liquid-crystal light valve with spatiotemporal modulated optical feedback. These states are nonlinear waves in which energy concentrates in a localized and oscillatory manner. The organization of the family of solutions is characterized as a function of the applied voltage. Close to the reorientation transition, an amplitude equation allows us to elucidate the origin of these localized states and establish their bifurcation diagram. Theoretical findings are in qualitative agreement with experimental observations. Our results open the possibility of manipulating localized states induced by light, which can be used to expand and improve the storage and manipulation of information.

Eradication of established human melanoma tumors in nude mice by antibody-directed effector cells.

The simultaneous injection of monoclonal antibody 9.2.27, directed against a chondroitin sulfate proteoglycan preferentially expressed on human melanoma cells, and 2 X 10(7) mononuclear splenocytes, eradicated established, progressively growing human melanoma tumors in nude mice. Neither splenocytes nor antibody alone achieved significant tumor regression. The cells responsible for tumor elimination are most likely natural killer (NK) cells: they are present in splenocytes of T cell-deficient nude mice, and cloned cells with NK activity are able to suppress tumor growth. Moreover, splenocytes treated with anti-asialo GM1 and complement or harvested from NK-deficient C57BL/6 beige mice did not cause tumor rejection. Furthermore, treatment of BALB/c nude mice just before injection with anti-asialo GM1 antiserum, which is known to eliminate NK activity in vivo, resulted in better tumor growth. In addition, evidence is presented that cells with NK activity are probably the effectors responsible for melanoma target cell lysis in vitro: Antibody-dependent and -independent cell-mediated lysis of M21 melanoma cells was suppressed when splenocytes were preincubated with complement and antibodies specific for cell surface antigens of NK cells, i.e., anti-asialo GM1, anti-Qa5, and anti-NK1.1. Moreover, splenocytes of C57BL/6 beige mice were not able to lyse M21 cells in vitro. These results strongly support the conclusion that cells with NK activity are indeed responsible for the antibody-dependent destruction of M21 melanoma cells in vivo and in vitro.

The role of hen's egg-specific IgE, IgG and IgG4 in the diagnostic procedure of hen's egg allergy.

BACKGROUND: Hen's egg (HE) allergy is a common disease in childhood. HE-specific serum IgE has been correlated with the outcome of oral food challenge tests, and diagnostic decision points have been described as helpful but still not sufficient to reduce the requirement for oral food challenges. The aim of the study was to correlate HE-specific IgE, IgG and IgG4 levels with the outcome of double-blind, placebo-controlled food challenges (DBPCFC) in patients with suspected HE allergy to improve diagnostic procedures. METHODS: HE-specific IgE, IgG, and IgG4 levels were compared between 150 children with suspected HE allergy based on sensitization and/or patient's history who underwent DBPCFC. Sixty-six patients were HE-allergic (HE-sensitized with a positive DBPCFC), 48 HE-sensitized but tolerant (negative DBPCFC), and 36 patients were nonsensitized and tolerant (negative DBPCFC). Prior to food challenge HE-specific serum IgE, IgG, and IgG4 were measured with the Phadia CAP-system. RESULTS: HE-specific IgE was significantly higher in HE-allergic patients than in clinically tolerant ones. However, there was no difference in HE-specific IgG and IgG4 concentrations between the patient groups. CONCLUSION: A proposed cut-off level of 12 kU/l IgE would identify children above this level correctly as HE-allergic. The level of HE-specific IgG or IgG4 in serum of children with suspected HE allergy does not add any additional information in the diagnostic procedure of HE allergy. For diagnostic purposes, specific IgG or IgG4 should not routinely be tested.

Prospective evaluation of 4-D contrast-enhanced-ultrasound (CEUS) imaging in bladder tumors.

PURPOSE: The evaluation of the potential clinical benefit of four-dimensional ultrasound (4D-US) in the assessment of bladder cancer (BC). MATERIAL AND METHODS: 20 patients with indication for cystoscopy for suspicion of bladder cancer were prospectively included in this study. All patients underwent two-dimensional ultrasound (2D-US), contrast enhanced ultrasound (CEUS) and real-time four-dimensional ultrasound (4D-US). All acquisitions were compared to each other in regard to image quality. This assessment was done using a 6 point scale (1 = best). All patients underwent subsequently cystoscopy with resection of the tumor (TURB), due a histopathological analysis was possible. RESULTS: All examinations were performed successfully and no patient had to be excluded from the study. Patients acceptance of 4D-US was consistently good. No adverse events occurred. Image quality of real time 4D-US (score: 1.27±0.46) was significantly superior (p < 0.001) to both, conventional 2D-US (score: 2.33±0.62) and also to 2D-CEUS (score: 2.00±0.53). In terms of tumor detection no superiority was evident for 4D-US compared to 2D-US or in utilization of CEUS (sensitivity = 0.89; specificity = 1.00; positive predictive value = 1.00; negative predictive value = 0.50; AUC = 0.944; (95% CI: 07.43-0.998)). CONCLUSION: The assessment of bladder cancer using real time 4D-US is feasible and improves the image quality and therefore also the precise anatomical consistency of intravesical tumor masses.

Structure and function of a squalene cyclase.

The crystal structure of squalene-hopene cyclase from Alicyclobacillus acidocaldarius was determined at 2.9 angstrom resolution. The mechanism and sequence of this cyclase are closely related to those of 2,3-oxidosqualene cyclases that catalyze the cyclization step in cholesterol biosynthesis. The structure reveals a membrane protein with membrane-binding characteristics similar to those of prostaglandin-H2 synthase, the only other reported protein of this type. The active site of the enzyme is located in a large central cavity that is of suitable size to bind squalene in its required conformation and that is lined by aromatic residues. The structure supports a mechanism in which the acid starting the reaction by protonating a carbon-carbon double bond is an aspartate that is coupled to a histidine. Numerous surface alpha helices are connected by characteristic QW-motifs (Q is glutamine and W is tryptophan) that tighten the protein structure, possibly for absorbing the reaction energy without structural damage.

Structure of the thiamine- and flavin-dependent enzyme pyruvate oxidase.

Pyruvate oxidase from Lactobacillus plantarum is a tetrameric enzyme that decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate. Structure determination at 2.1 angstroms showed that the cofactors thiamine pyrophosphate (TPP) and flavin adenine dinucleotide (FAD) are bound at the carboxyl termini of six-stranded parallel beta sheets. The pyrophosphate moiety of TPP is bound to a metal ion and to a beta alpha alpha beta unit corresponding to an established sequence fingerprint. The spatial arrangement of TPP and FAD suggests that the oxidation of the oxyethyl intermediate does not occur by hydride displacement but rather by a two-step transfer of two electrons.

Molecular architecture and electrostatic properties of a bacterial porin.

The integral membrane protein porin from Rhodobacter capsulatus consists of three tightly associated 16-stranded beta barrels that give rise to three distinct diffusion channels for small solutes through the outer membrane. The x-ray structure of this porin has revealed details of its shape, the residue distributions within the pore and at the membrane-facing surface, and the location of calcium sites. The electrostatic potential has been calculated and related to function. Moreover, potential calculations were found to predict the Ca2+ sites.

[Follow-up surveillance of muscle-invasive urinary bladder cancer after curative treatment]. / Nachsorge des muskelinvasiven Harnblasenkarzinoms nach kurativer Therapie.

Follow-up care of patients with muscle-invasive bladder cancer is subdivided into oncological and functional surveillance. More than 80% of local relapses and distant metastases occur within the first 2 years. Recurrences in the remnant urothelium also occur several years after radical cystectomy. Urinary cytology and a computed tomography (CT) scan of the abdomen and thorax including a urography phase are the standard diagnostics for tumor follow-up. There is no clear evidence for a survival benefit for the detection of asymptomatic vs. symptomatic recurrences. After partial cystectomy or trimodal treatment, there is no established follow-up schedule; however, the relatively high incidence of intravesical recurrences should be considered as there are curative treatment approaches including salvage cystectomy. Functional surveillance, which should be carried out lifelong, encompasses prevention and diagnostics of metabolic complications, urethral/ureteral strictures, problems with the urinary stoma, urinary incontinence, sexual dysfunction and urinary tract infections.

[Aftercare of non-muscle invasive bladder cancer]. / Nachsorge des nicht muskelinvasiven Harnblasenkarzinoms.

Tumor follow-up in patients with non-muscle invasive bladder cancer (NMIBC) is a weighing up between the morbidity associated with invasive diagnostics and the risk of tumor recurrence and especially progression. The risk stratification into low, intermediate, and high-risk tumors enables a risk-adapted follow-up. For individual estimation of the risk of progression and recurrence, risk calculators should be used. Follow-up is still based on cystoscopy, which is recommended lifelong for high and intermediate-risk tumors and for up to 5 tumor-free years for low-risk tumors. Urine cytology has a high sensitivity and specificity for high-risk tumors and is recommended in the follow-up care. There is currently no recommendation for any commercially available urinary marker due to inadequate evidence. For the clarification of synchronous and metachronous tumors of the upper urinary tract computed tomography (CT) urography or alternatively magnetic resonance (MR) urography is recommended.

[Follow-up of renal cell carcinoma in a nonmetastatic stage]. / Nachsorge beim Nierenzellkarzinom im nicht fernmetastasierten Stadium.

Postoperative follow-up care after curative surgery or ablative treatment is the standard of care in patients with nonmetastatic renal cell carcinoma. The goal is to identify and treat postoperative complications and local recurrences early on. Follow-up investigations and their relevance are widely acknowledged and validated and patients undergoing follow-up seem to benefit from a longer survival in nonmetastatic renal cell carcinoma. Hence there is no consensus on a standardized follow-up strategy. The most disputed question is around the frequency of the investigations and the duration of the follow-up. Without an evidence-based follow-up protocol, urologists should carry out an individualized, potentially lifelong follow-up regimen, which also includes the patients' needs and perspectives.

[Value of imaging in upper urinary tract tumors]. / Wertigkeit der Bildgebung bei Tumoren des oberen Harntraktes.

BACKGROUND: Staging of bladder cancer, hematuria as well as the evaluation of unclear findings of the kidneys and ureters are the most frequent indications for imaging of the upper urinary tract (UUT). Endourological assessment of the UUT is much more invasive compared to imaging of the bladder, raising the question of the optimal imaging technique. Several technical improvements regarding computed tomography (CT) as well as magnetic resonance imaging (MRI) were implemented in recent years. OBJECTIVES: To compare the efficacy and limitations of the most important imaging techniques regarding the UUT. MATERIALS AND METHODS: Systematic review of the literature and current German, European, and American guidelines regarding bladder cancer, urothelial carcinoma of the UUT and hematuria. RESULTS: The CT-based urography has superseded excretory urography and is the first choice for imaging of the UUT. In case of contraindications, MRI is a feasible alternative. In all cases, a urography phase is indispensable. CONCLUSIONS: Imaging of the UUT has to be used in a reasonable combination together with endourological methods and cytology. Optical coherence tomography, confocal laser endomicroscopy and scientific innovations such as radiomics might improve UUT imaging and differential diagnosis of UUT lesions in the future.

beta-Barrel membrane proteins.

beta-Barrel proteins are found in the outer membranes of bacteria, mitochondria and chloroplasts. The presently known sizes range from small eight-stranded to large twenty-two-stranded beta barrels existing as monomers and oligomers. Their functions are as diverse as active ion transport, passive nutrient intake, membrane anchors, membrane-bound enzymes and defense against attack proteins. Of further interest are the folding process, the crystallization, the observed limited structural diversity and the manifold channel engineering options of these beta-barrel proteins.

Porins: general to specific, native to engineered passive pores.

Several porins from bacterial outer membranes have been crystallized and analyzed by X-ray diffraction, yielding a consistent picture of these membrane-channel proteins. The structures of general and specific channels are in agreement with electrophysiological, diffusional and biochemical data, and provide a starting point for the engineering of other passive membrane pores or porins with new selectivities.

Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis.

SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests. RESULTS: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI. CONCLUSIONS: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Risks and benefits of pelvic lymphadenectomy in octogenarians undergoing radical cystectomy due to urothelial carcinoma of the bladder.

OBJECTIVES: According to current guidelines, radical cystectomy (RC) should be combined with an extended pelvic lymphadenectomy (PLND) as therapeutic and staging instrument. Objective of this study was to analyze the influence of PLND on survival rates and complication rates in a selected group of elderly patients with a minimum age of 80 years. MATERIALS AND METHODS: In this single-center retrospective analysis, we evaluated 102 patients who underwent RC due to UCB from 2004 to 2015 at our institution. In 74 patients (73%), RC was combined with PLND; in 28 cases (27%), RC was performed without PLND. Impact of PLND on cancer specific survival (CSS), overall survival (OS) and progression-free survival (PFS) was analyzed using log-rank test and COX regression model. RESULTS: In univariate analysis of the data, we were not able to show a significant impact of PLND on CSS (p = 0.606), OS (p = 0.979) or PFS (p = 0.883). Also in multivariate analysis of the data, we were not able to identify PLND as an independent prognostic parameter on survival rates of patients undergoing RC, neither for CSS (p = 0.912) nor OS (p = 0.618) or PFS (p = 0.900). CONCLUSIONS: Our small and single-center study was not able to demonstrate a significant independent influence of PLND on CSS, OS and PFS in octogenarians undergoing RC due to UCB. There is no doubt that RC should usually be combined with PLND, but the results of this small data set with a selected patient cohort indicate that RC without PLND might be an option in selected cases of elderly patients.