bluuebunny/crossref_metadata_2025 huggingface dataset:
Protosappanin B promotes apoptosis and causes G1 cell cycle arrest in human bladder cancer cells
Authors: Yang Xihua , Zhao Lili , Zhang Tingting , Xi Junfeng , Liu Shuze , Ren Liansheng , Zheng Yaqin , Zhang Huanhu
Published: January 2019

The aim of the study was to investigate the effects of protosappanin B on the proliferation and apoptosis of bladder cancer cells. The effects of protosappanin B (12.5, 25, 50, 100, or 200 μg/mL, 48 h) on proliferation of SV-HUC-1, T24 and 5637 cells was assessed using the MTT assay. The effects of protosappanin B (100, 150, 200, 250, or 300 μg/mL, 48 h) on cell apoptosis and cell cycle were analyzed using flow cytometry. T24 and 5637 cells treated with 200 µg/mL protosappanin B showed morphological changes (shrinkage, rounding, membrane abnormalities, and reduced adhesion), but protosappanin B had no proliferation arrest effect on SV-HUC-1 cells. Protosappanin B caused concentration-dependent inhibition of cell growth, with IC50 of 82.78 µg/mL in T24 cells and 113.79 µg/mL in 5637 cells. Protosappanin B caused concentration-dependent increases in T24 and 5637 cell apoptosis (100–300 µg/mL). The effects of protosappanin B on the cell cycle in both cell types was G1 arrest with reductions in the proportion of S-phase cells and proliferation index. A proteomics analysis showed that protosappanin B modulated a number of genes involved in the cell cycle. In conclusion, protosappanin B inhibits the proliferation and promotes the apoptosis of T24 and 5637 human bladder cancer cells in a concentration-dependent manner, possibly via interference with cell cycle regulation, preventing G1-to-S transition.
Fundamental noisy multiparameter quantum bounds
Authors: Roy Shibdas
Published: January 2019

Quantum multiparameter estimation involves estimating multiple parameters simultaneously and can be more precise than estimating them individually. Our interest here is to determine fundamental quantum limits to the achievable multiparameter estimation precision in the presence of noise. We first present a lower bound to the estimation error covariance for a noisy initial probe state evolving through a noiseless quantum channel. We then present a lower bound to the estimation error covariance in the most general form for a noisy initial probe state evolving through a noisy quantum channel. We show conditions and accordingly measurements to attain these estimation precision limits for noisy systems. We see that the Heisenberg precision scaling of 1/N can be achieved with a probe comprising N particles even in the presence of noise. In fact, some noise in the initial probe state or the quantum channel can serve as a feature rather than a bug, since the estimation precision scaling achievable in the presence of noise in the initial state or the channel in some situations is impossible in the absence of noise in the initial state or the channel. However, a lot of noise harms the quantum advantage achievable with N parallel resources, and allows for a best precision scaling of $${\bf{1}}/\sqrt{{\boldsymbol{N}}}$$
1
/

N

. Moreover, the Heisenberg precision limit can be beaten with noise in the channel, and we present a super-Heisenberg precision limit with scaling of 1/N2 for optimal amount of noise in the channel, characterized by one-particle evolution operators. Furthermore, using γ-particle evolution operators for the noisy channel, where γ > 1, the best precision scaling attainable is 1/N2γ, which is otherwise known to be only possible using 2γ-particle evolution operators for a noiseless channel.
Optimising the detectability of H5N1 and H5N6 highly pathogenic avian influenza viruses in Vietnamese live-bird markets
Authors: Vergne Timothée , Meyer Anne , Long Pham Thanh , Elkholly Doaa A. , Inui Ken , Padungtod Pawin , Newman Scott H. , Fournié Guillaume , Pfeiffer Dirk U.
Published: January 2019

Live bird markets (LBMs) are major targets for avian influenza virus (AIV) surveillance programmes. While sampling the LBM environment has become a widely used alternative to the labour-intensive sampling of live poultry, the design of surveillance programmes and the interpretation of their results are compromised by the lack of knowledge about the effectiveness of these sampling strategies. We used latent class models and a unique empirical dataset collated in Vietnamese LBMs to estimate the sensitivity and specificity of five different sample types for detecting AIVs subtypes H5N1 and H5N6: oropharyngeal duck samples, solid and liquid wastes, poultry drinking water and faeces. Results suggest that the sensitivity of environmental samples for detecting H5N1 viruses is equivalent to that of oropharyngeal duck samples; however, taking oropharyngeal duck samples was estimated to be more effective in detecting H5N6 viruses than taking any of the four environmental samples. This study also stressed that the specificity of the current surveillance strategy in LBMs was not optimal leading to some false positive LBMs. Using simulations, we identified 42 sampling strategies more parsimonious than the current strategy and expected to be highly sensitive for both viruses at the LBM level. All of these strategies involved the collection of both environmental and oropharyngeal duck samples.
HPLC methods for purity evaluation of man-made single-stranded RNAs
Authors: Kanavarioti Anastassia
Published: January 2019

Synthetic RNA oligos exhibit purity decreasing as a function of length, because the efficiency of the total synthesis is the numerical product of the individual step efficiencies, typically below 98%. Analytical methods for RNAs up to the 60 nucleotides (nt) have been reported, but they fall short for purity evaluation of 100nt long, used as single guide RNA (sgRNA) in CRISPR technology, and promoted as pharmaceuticals. In an attempt to exploit a single HPLC method and obtain both identity as well as purity, ion-pair reversed-phase chromatography (IP-RP) at high temperature in the presence of an organic cosolvent is the current analytical strategy. Here we report that IP-RP is less suitable compared to the conventional ion-exchange (IEX) for analysis of 100nt RNAs. We demonstrate the relative stability of RNA in the denaturing/basic IEX mobile phase, lay out a protocol to determine the on-the-column stability of any RNA, and establish the applicability of this method for quality testing of sgRNA, tRNA, and mRNA. Unless well resolving HPLC methods are used for batch-to-batch evaluation of man-made RNAs, process development will remain shortsighted, and observed off-target effects in-vitro or in-vivo may be partially related to low purity and the presence of shorter sequences.
Prognostic Factors and Visual Outcomes of Pyogenic Liver Abscess-Related Endogenous Klebsiella pneumoniae Endophthalmitis: A 20-year retrospective review
Authors: Chen Yi-Hua , Li Ya-Han , Lin Yu-Jr , Chen Yen-Po , Wang Nan-Kai , Chao An-Ning , Liu Laura , Wu Wei-Chi , Lai Chi-Chun , Chen Tun-Lu , Chen Kuan-Jen
Published: January 2019

Endogenous K. pneumoniae endophthalmitis (EKE) has a higher incidence among East Asians, and the most common infectious source of EKE is pyogenic liver abscess (PLA). We investigate the risk factors for poor visual outcomes in patients with PLA-related EKE. The retrospective medical records of 104 patients (120 eyes) diagnosed with PLA-related EKE between 1996 and 2015. In univariate logistic regression analysis, the risk factors for poor visual outcomes were initial visual acuity (VA) worse than counting fingers (CF) (p < 0.001), eye pain (p = 0.013), hypopyon (p = 0.003), ocular hypertension (p = 0.003), positive intraocular fluids cultures (p < 0.001), subretinal abscess (p = 0.025), unilateral involvement (p = 0.017), delayed ophthalmologic visit (p = 0.022), initially presented with ocular symptoms ahead of systemic symptoms (p < 0.001), and corneal edema (p < 0.001). Intravitreal dexamethasone reduced the requirement of enucleation or evisceration (p = 0.01). The multivariate logistic regression revealed that poor initial VA worse than CF (p = 0.004) and initially presented with ocular symptoms ahead of systemic symptoms (p = 0.007) were the significant independent factors for poor visual outcomes. Early diagnosis and prompt treatment may salvage useful vision in some eyes.
Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy
Authors: Sprissler Ryan , Bina Robert , Kasoff Willard , Witte Marlys H. , Bernas Michael , Walter Christina , Labiner David M. , Lau Branden , Hammer Michael F. , Weinand Martin E.
Published: January 2019

Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value < 0.05, FDR <0.05). Network and pathway analyses identified differential activation of pathways involved in lipid metabolism, morphology of oligodendrocytes, inflammatory response, and development of astrocytes. These results suggest that pre-operative leukocyte expression profiles have prognostic value for seizure outcome following SLAH.
Robust epidermal tattoo electrode platform for skin physiology monitoring
Authors: De Guzman Keana , Al-Kharusi Ghayadah , Levingstone Tanya , Morrin Aoife
Published: January 2019

Robustness in an impedance-based tattoo electrode platform is achieved through the integration of novel material approaches for skin physiology monitoring.
In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes
Authors: Velozo-Sá Vivianne S. , Pereira Luciano R. , Lima Aliny P. , Mello-Andrade Francyelli , Rezende Manuela R. M. , Goveia Rebeca M. , Pires Wanessa C. , Silva Monize M. , Oliveira Katia M. , Ferreira Antonio G. , Ellena Javier , Deflon Victor M. , Grisolia Cesar Koppe , Batista Alzir A. , Silveira-Lacerda Elisângela P.
Published: January 2019

Ru(ii)/2-mercaptopyrimidine complexes active against cancer cells did not present toxic effects during embryonic and larval development of zebrafish.
Synthesis of (E)-1,4-disilsesquioxylsubstituted but-1-en-3-ynes via platinum-catalyzed dimerization of ethynylsiloxysilsesquioxanes
Authors: Żak Patrycja , Bołt Małgorzata , Dudziec Beata , Kubicki Maciej
Published: January 2019

The [Pt(IPr*Ph)(dvtms)] complex efficiently catalyzes the E-selective dimerization of ethynylsiloxysilsesquioxanes leading to a novel class of silsesquioxane derivatives, resembling their dumbbell-shaped analogues.
Impact of a sustained consumption of grape extract on digestion, gut microbial metabolism and intestinal barrier in broiler chickens
Authors: Chamorro Susana , Romero Carlos , Brenes Agustín , Sánchez-Patán Fernando , Bartolomé Begoña , Viveros Agustín , Arija Ignacio
Published: January 2019

Escherichia coli, Enterobacteriaceae and lactic-acid bacteria ileal counts were reduced in birds fed GE.
Cell motility dependence on adhesive wetting
Authors: Cao Yuansheng , Karmakar Richa , Ghabache Elisabeth , Gutierrez Edgar , Zhao Yanxiang , Groisman Alex , Levine Herbert , Camley Brian A. , Rappel Wouter-Jan
Published: January 2019

Adhesive cell–substrate interactions are crucial for cell motility and increasing the adhesion results in increased cell spreading and cell speed.
Destabilizing effect of perfluorodecanoic acid on simple membrane models
Authors: Viada Benjamin , Cámara Candelaria I. , Yudi Lidia M.
Published: January 2019

The surfactant perfluorodecanoic acid (PFD), widely used in different industrial applications and an important environmental contaminant, can penetrate distearoyl phosphatidic acid (DSPA), dilauroyl phosphatidic acid (DLPA) and distearoyl phosphatidylethanolamine (DSPE) monolayers, even at high pressures values, above 30 mN m−1, which is the accepted lateral pressure value for a cellular bilayer.
Ultrathin MoS2 nanosheets homogenously embedded in a N,O-codoped carbon matrix for high-performance lithium and sodium storage
Authors: Han Meisheng , Lin Zijia , Yu Jie
Published: January 2019

Ultrathin MoS2 nanosheets uniformly embedded into a N,O-codoped carbon matrix possess outstanding cyclability and rate performances as a lithium/sodium ion battery anode.
Optimized orientation and enhanced thermoelectric performance in Sn0.97Na0.03Se with Te addition
Authors: Zhang Jiahua , Xu Jingtao , Tan Xiaojian , Wang Hongxiang , Liu Guo-Qiang , Shao Hezhu , Yu Bo , Yue Song , Jiang Jun
Published: January 2019

An unconventional liquid-phase compaction method was used to prepare Sn0.97Na0.03Se thermoelectric materials, leading to high oritentation with excellent electrical properties.
Morphology, composition and selectivity of nickel/titanium oxide nanoflakes grown on a superelastic nickel/titanium alloy fiber substrate for highly efficient solid-phase microextraction of aromatic compounds
Authors: Du Junliang , Wang Feifei , Wang Zhuo , Wang Xuemei , Du Xinzhen
Published: January 2019

Direct in situ hydrothermal growth of nickel/titanium oxide nanoflakes was carried out on superelastic nickel/titanium alloy wires for solid-phase microextraction.
Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate
Authors: He Haiqing , Chen Dong , Li Xiaomei , Li Chengji , Zhao Jin-Hua , Qin Hong-Bo
Published: January 2019

A synthesis of repeating unit of trisaccharide, complete stereoselectivity of glycosylation and flexible synthetic strategy.
Copper-catalyzed carbene/alkyne metathesis terminated with the Buchner reaction: synthesis of dihydrocyclohepta[b]indoles
Authors: Zeng Qian , Dong Kuiyong , Huang Jingjing , Qiu Lihua , Xu Xinfang
Published: January 2019

A copper-catalyzed carbene/alkyne metathesis reaction of alkyne-tethered diazoacetates is reported, which provides dihydrocyclohepta[b]indole skeletons under mild reaction conditions.
Bioinformatics analysis to identify the key genes affecting the progression and prognosis of hepatocellular carcinoma
Authors: Zhang Yingai , Wang Shunlan , Xiao Jingchuan , Zhou Hailong
Published: January 2019

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, which has poor outcome. The present study aimed to investigate the key genes implicated in the progression and prognosis of HCC. The RNA-sequencing data of HCC was extracted from The Cancer Genome Atlas (TCGA) database. Using the R package (DESeq), the differentially expressed genes (DEGs) were analyzed. Based on the Cluepedia plug-in in Cytoscape software, enrichment analysis for the protein-coding genes amongst the DEGs was conducted. Subsequently, protein–protein interaction (PPI) network was built by Cytoscape software. Using survival package, the genes that could distinguish the survival differences of the HCC samples were explored. Moreover, quantitative real-time reverse transcription-PCR (qRT-PCR) experiments were used to detect the expression of key genes. There were 2193 DEGs in HCC samples. For the protein-coding genes amongst the DEGs, multiple functional terms and pathways were enriched. In the PPI network, cyclin-dependent kinase 1 (CDK1), polo-like kinase 1 (PLK1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), serum amyloid A1 (SAA1), and lysophosphatidic acid receptor 3 (LPAR3) were hub nodes. CDK1 interacting with PLK1 and FOS, and LPAR3 interacting with FOS and SAA1 were found in the PPI network. Amongst the 40 network modules, 4 modules were with scores not less than 10. Survival analysis showed that anterior gradient 2 (AGR2) and RLN3 could differentiate the high- and low-risk groups, which were confirmed by qRT-PCR. CDK1, PLK1, FOS, SAA1, and LPAR3 might be key genes affecting the progression of HCC. Besides, AGR2 and RLN3 might be implicated in the prognosis of HCC.
Descriptive Analysis of the Interactive Patterning of the Vocalization Subsystems in Healthy Participants: A Dynamic Systems Perspective
Authors: Croake Daniel J. , Andreatta Richard D. , Stemple Joseph C.
Published: January 2019

Purpose

Normative data for many objective voice measures are routinely used in clinical voice assessment; however, normative data reflect vocal output, but not vocalization process. The underlying physiologic processes of healthy phonation have been shown to be nonlinear and thus are likely different across individuals. Dynamic systems theory postulates that performance behaviors emerge from the nonlinear interplay of multiple physiologic components and that certain patterns are preferred and loosely governed by the interactions of physiology, task, and environment. The purpose of this study was to descriptively characterize the interactive nature of the vocalization subsystem triad in subjects with healthy voices and to determine if differing subgroups could be delineated to better understand how healthy voicing is physiologically generated.

Method

Respiratory kinematic, aerodynamic, and acoustic formant data were obtained from 29 individuals with healthy voices (21 female and eight male). Multivariate analyses were used to descriptively characterize the interactions among the subsystems that contributed to healthy voicing.

Results

Group data revealed representative measures of the 3 subsystems to be generally within the boundaries of established normative data. Despite this, 3 distinct clusters were delineated that represented 3 subgroups of individuals with differing subsystem patterning. Seven of the 9 measured variables in this study were found to be significantly different across at least 1 of the 3 subgroups indicating differing physiologic processes across individuals.

Conclusion

Vocal output in healthy individuals appears to be generated by distinct and preferred physiologic processes that were represented by 3 subgroups indicating that the process of vocalization is different among individuals, but not entirely idiosyncratic. Possibilities for these differences are explored using the framework of dynamic systems theory and the dynamics of emergent behaviors. A revised physiologic model of phonation that accounts for differences within and among the vocalization subsystems is described.

Supplemental Material

https://doi.org/10.23641/asha.7616462
Improved disturbance detection and load shedding technique for low voltage islanded microgrids
Authors: Arunan Anusuya , Ravishankar Jayashri , Ambikairajah Eliathamby
Published: January 2019

The rate of change of frequency (RoCoF) following any disturbance in low voltage islanded microgrids is not only relatively high compared to conventional systems, but also becomes location specific due to the presence of highly resistive lines. This makes the disturbance detection challenging. A novel real‐time disturbance detection technique for low voltage islanded microgrids is proposed that is independent of the system inertia, which can detect any disturbance within 100 ms. A dedicated initial RoCoF calculation is developed over a 30 ms window especially during disturbances. The authors use a support vector machine‐based regression model for the estimation of the amount of disturbance with three different feature selections. These models prove that only the RoCoF is not enough to estimate the amount of disturbance in an islanded microgrid and additional features from the frequency and different bus voltages also required. A load shedding algorithm encompassing battery support is also proposed to protect the system from quick frequency collapse by providing power from the battery when the frequency reaches its standard operational limit. All the proposed algorithms are tested with a low voltage islanded microgrid modelled in MATLAB/SIMULINK. The results are also verified with noisy data to reflect real system performance.
Simultaneous consideration of the balancing market and day‐ahead market in Stackelberg game for flexiramp procurement problem in the presence of the wind farms and a DR aggregator
Authors: Kaheh Zohreh , Kazemzadeh Reza Baradaran , Sheikh‐El‐Eslami Mohammad Kazem
Published: January 2019

This study presents a cooperative bidding model for energy, reserve, and flexiramp providing by a group of suppliers. Procurement problems in electricity markets have been analysed through the Stackelberg concept and modelled via bi‐level programming. However, previous bi‐level models have captured the game only in the context of the day‐ahead or real‐time market. In this study, a stochastic two‐stage multi‐objective bi‐level model for procurement problem in the day‐ahead and balancing markets is proposed; in which the Stackelberg game is simultaneously considered in these markets. In each stage of the proposed model, multiple decision‐makers including conventional and wind generating units as well as a demand response (DR) aggregator act as leaders, and independent system operator (ISO) acts as a follower. The presented model for DR aggregator determines some important parameters dynamically considering the hourly locational marginal prices and the behaviour of the small‐size consumers. To solve the model, two reformulation schemes are presented: (i) a Karush Kuhn Tucker (KKT) method with some linearisation approaches and (ii) a fuzzy max–min technique. The proposed model is applied to the 24‐bus IEEE test system to demonstrate the effects of the Stackelberg game in balancing market on the day‐ahead market's equilibriums and benefits of implementing the proposed model in electricity markets.
The quest for stellar coronal mass ejections in late-type stars
Authors: Vida Krisztián , Leitzinger Martin , Kriskovics Levente , Seli Bálint , Odert Petra , Kovács Orsolya Eszter , Korhonen Heidi , van Driel-Gesztelyi Lidia
Published: January 2019

Context. Flares and coronal mass ejections (CMEs) can have deleterious effects on their surroundings: they can erode or completely destroy atmospheres of orbiting planets over time and also have high importance in stellar evolution. Most of the CME detections in the literature are single events found serendipitously sparse for statistical investigation.

Aims. We aimed to gather a large amount of spectral data of M-dwarfs to drastically increase the number of known events to make statistical analysis possible in order to study the properties of potential stellar CMEs.

Methods. Using archival spectral data we investigated asymmetric features of Balmer-lines, which could indicate the Doppler-signature of ejected material.

Results. Of more than 5500 spectra we find 478 that have line asymmetries – including nine larger events, in terms of velocity and mass – on 25 objects, with 1.2–19.6 events per day on objects with line asymmetries. Most events are connected with enhanced peaks of Balmer-lines, indicating that these are connected to flares similar to solar events. In most cases the detected speed does not reach surface escape velocity: the typical observed maximum velocities are on the order of 100–300 km s−1, while the typical masses of the ejecta were on the order of 1015−1018 g. Statistical analysis of the events suggests that these events are more frequent on cooler stars with stronger chromospheric activity.

Conclusions. If the detected events correspond to CMEs, the detected maximum velocities are lower than those observed on the Sun, while event rates were somewhat lower than we could expect from the solar case. If the velocities are not distorted significantly due to a projection effect, these findings may support the idea that most of the coronal mass ejections could be suppressed by a strong magnetic field. Alternatively, it is possible that we can observe only an early low-coronal phase of the events before being accelerated at higher altitudes. Our findings could indicate that later-type, active dwarfs could be a safer environment for exoplanetary systems CME-wise than previously thought, and atmosphere loss due to radiation effects would play a stronger role in exoplanetary atmosphere evolution than CMEs.
Optimized transit detection algorithm to search for periodic transits of small planets
Authors: Hippke Michael , Heller René
Published: January 2019

We present a new method to detect planetary transits from time-series photometry, the transit least squares (TLS) algorithm. TLS searches for transit-like features while taking the stellar limb darkening and planetary ingress and egress into account. We have optimized TLS for both signal detection efficiency (SDE) of small planets and computational speed. TLS analyses the entire, unbinned phase-folded light curve. We compensated for the higher computational load by (i.) using algorithms such as “Mergesort” (for the trial orbital phases) and by (ii.) restricting the trial transit durations to a smaller range that encompasses all known planets, and using stellar density priors where available. A typical K2 light curve, including 80 d of observations at a cadence of 30 min, can be searched with TLS in ∼10 s real time on a standard laptop computer, as fast as the widely used box least squares (BLS) algorithm. We perform a transit injection-retrieval experiment of Earth-sized planets around sun-like stars using synthetic light curves with 110 ppm white noise per 30 min cadence, corresponding to a photometrically quiet KP = 12 star observed with Kepler. We determine the SDE thresholds for both BLS and TLS to reach a false positive rate of 1% to be SDE = 7 in both cases. The resulting true positive (or recovery) rates are ∼93% for TLS and ∼76% for BLS, implying more reliable detections with TLS. We also test TLS with the K2 light curve of the TRAPPIST-1 system and find six of seven Earth-sized planets using an iterative search for increasingly lower signal detection efficiency, the phase-folded transit of the seventh planet being affected by a stellar flare. TLS is more reliable than BLS in finding any kind of transiting planet but it is particularly suited for the detection of small planets in long time series from Kepler, TESS, and PLATO. We make our python implementation of TLS publicly available.
Aktuelle Therapiestandards primärer ZNS-Lymphome
Authors: Schorb Elisabeth , Illerhaus Gerald , Finke Jürgen
Published: January 2019

Was ist neu?

Induktionstherapie Die weltweit größte Studie mit einem randomisierten Vergleich verschiedener Induktionstherapien zeigte, dass die Hinzunahme von Thiotepa und Rituximab zu einer hochdosierten Methotrexat- (MTX) und Cytarabin- (AraC) Therapie (sogenanntes MATRix-Protokoll) sowohl Ansprechen als auch Gesamtüberleben von Patienten mit Erstdiagnose eines primären ZNS-Lymphoms (PZNSL) verbessert. Die MATRix-Kombination gilt seither in Deutschland und international als neuer Behandlungsstandard. Aktuelle retrospektive Daten belegen die gute Wirksamkeit und Verträglichkeit nicht nur im Rahmen klinischer Studien, sondern auch im klinischen Alltag.

Konsolidierungstherapie In den vergangenen Jahren spielt die Hochdosistherapie mit nachfolgender autologer Stammzelltransplantation (HDT-ASZT) als Teil der Erstlinientherapie von Patienten mit PZNSL eine immer wichtigere Rolle. Im Rahmen zweier kürzlich vorgestellter randomisierter Studien wurde bestätigt, dass die HDT-ASZT mit einem 2-Jahres-Gesamtüberleben > 80 % einen effektiven Therapieansatz darstellt.

Ältere Patienten Aktuelle Daten aus Deutschland belegen die Effektivität einer Therapie mit hochdosiertem MTX in Kombination mit Rituximab und Procarbazin, gefolgt von Erhaltungstherapie mit Procarbazin (PRIMAIN-Protokoll). Retrospektive Daten sowie erste Ergebnisse einer prospektiven Studie zeigen außerdem, dass fitte Patienten > 65 Jahre von einer intensiveren Therapie inklusive HDT-ASZT profitieren können.

Therapie bei Rezidiv/refraktärem Verlauf Daten einer kürzlich publizierten Studie zeigen bei Patienten bis 66 Jahre Ansprechraten von bis zu 50 % nach Konsolidierungstherapie mittels Thiotepa-basierter HDT-ASZT. Randomisierte Studien zur Rezidivtherapie beim PZNSL liegen derzeit nicht vor.

Zielgerichtete Substanzen In den vergangenen Jahren wurden verschiedene Substanzen wie z. B. Lenalidomid und Pomalidomid sowie Ibrutinib mit vielversprechenden Ergebnissen in klinischen Studien untersucht. Aktuell ist in Deutschland noch keine Substanz für die zielgerichtete Therapie von Patienten mit PZNSL zugelassen.

Ausblick Intensive Induktionsstrategien sowie die konsolidierende HDT-ASZT stellen zunehmend den Therapiestandard dar. Aktuell laufen weitere große klinische Studien zum Stellenwert der HDT-ASZT sowohl bei jüngeren Patienten im Vergleich zu einer konventionellen Chemotherapie als auch bei älteren Patienten als kurativer Therapieansatz. Zusätzlich werden in Kürze neue Daten zum Einsatz zielgerichteter Substanzen erwartet.
Das diabetische Herz und Herzinsuffizienz – Aktuelles zu Entstehung und Therapie
Authors: Zweck Elric , Szendrödi Julia , Kelm Malte , Roden Michael
Published: January 2019

Was ist neu?

Klinisches Bild Typ-2-Diabetes-mellitus (T2 D) ist ein unabhängiger Risikofaktor für Herzinsuffizienz, die als Komplikation oftmals unterschätzt wird. Bei T2 D kann sich früh eine diastolische Funktionsstörung ausbilden, die sich später zu einer Herzinsuffizienz entwickeln kann. Von einer ischämischen Kardiomyopathie ist eine Diabetes-bedingte Herzinsuffizienz aktuell nicht abgrenzbar.

Pathophysiologie Hyperglykämie, Hyperinsulinämie und Hyperlipidämie bei T2 D verändern den myokardialen Stoffwechsel. Daraus resultieren oxidativer Stress, reduzierte mitochondriale Effizienz, Lipotoxizität und Apoptose im Herzen. Die T2D-assoziierte nicht-alkoholische Fettlebererkrankung (NAFLD) zeigt ähnliche Pathomechanismen und stellt einen potenziellen Risikofaktor dar.

Therapiestrategien Zur Verbesserung der Herzfunktion wird die Kontrolle kardiovaskulärer Risikofaktoren sowie Reduktion der Insulinresistenz durch Bewegung und Gewichtsabnahme empfohlen. Neben Metformin scheinen SGLT2-Inhibitoren als zusätzliche Therapieoption besonders geeignet zu sein. Auch die NAFLD könnte ein Angriffspunkt zukünftiger Therapieansätze werden.
Prävention, Diagnostik und Behandlung von Gallensteinen
Authors: Lammert Frank , Gutt Carsten
Published: January 2019

Was ist neu?

Prävention von Gallensteinen Lifestyleänderungen im Sinne von regelmäßiger körperlicher Aktivität und bedarfsgerechter Ernährung können der Entwicklung von Cholesteringallenblasensteinen vorbeugen. Ursodeoxycholsäure sollte bei ABCB4-Defizienz präventiv eingesetzt werden.

Diagnostik Der Nachweis einer akuten Cholezystitis soll primär sonografisch in Kombination mit den klinischen Befunden erfolgen. Die Endosonografie sollte bei unklaren Fällen wegen ihrer hohen Sensitivität und Spezifität für Gallengangsteine eingesetzt werden.

Therapie Die medikamentöse Therapie der biliären Kolik sollte mit nichtsteroidalen Antiphlogistika erfolgen. Die akute Cholezystitis stellt eine Indikation zur frühzeitigen (innerhalb von 24 Stunden nach stationärer Aufnahme) laparoskopischen Cholezystektomie dar. Nach ERC bei Choledocholithiasis sollte bei Cholezystolithiasis eine frühe (innerhalb von 72 Stunden) Cholezystektomie durchgeführt werden, ebenso nach milder biliärer Pankreatitis (während desselben stationären Aufenthalts).
Fortschritte bei der Systemischen Sklerose
Authors: Riemekasten Gabriela
Published: January 2019

Was ist neu?

Von der Pathogenese zu neuen therapeutischen Zielen Das adaptive Immunsystem scheint für die Pathogenese entscheidend. Insbesondere dürften Autoantikörper, die das angeborene und adaptive Immunsystem regulieren, eine wesentliche Rolle spielen.

Das frühe Erkennen von Organkomplikationen Schäden entstehen in den ersten 5 Jahren nach Beginn des Raynaud-Syndroms. Daher ist ein kontinuierliches Screening auf Organschäden nötig; die frühe Zuweisung in Zentren wird empfohlen. Bei Polymerase-III-Ak muss an ein paraneoplastisches Syndrom gedacht werden. Die kardiale Beteiligung ist prognostisch wichtiger als zuvor vermutet.

Besseres Verstehen der Krankheitslast Die Systemische Sklerose (SSc) besitzt eine Vielzahl von wenig bekannten Symptomen wie Inkontinenz, Juckreiz und beeinträchtigt in der Regel die Lebensqualität deutlich.

Die Letalität der Systemischen Sklerose D ie Mehrzahl der Patienten stirbt an der Erkrankung oder an deren Folgen, wobei neben der Lungenfibrose und der pulmonalen arteriellen Hypertonie die kardiale Beteiligung die knapp 10 %ige Sterblichkeit innerhalb von 2 Jahren verursacht. Durch frühes Erkennen von ventrikulären Tachykardien kann der plötzliche Herztod verhindert werden.

Neues zur Therapie der Systemischen Sklerose Frühe und intensive Therapien und die Behandlung in Zentren sind nötig. Bei früher diffuser SSc ist eine autologe Stammzelltransplantation zu erwägen. Eine Reihe Substanzen befindet sich derzeit in Phase-III-Studien. Viele SSc-Patienten sind untertherapiert.
Medikamentöse Therapie der Alzheimer-Demenz mit Antidementiva
Authors: Hausner Lucrezia , Frölich Lutz
Published: January 2019

Was ist neu?

Das Konzept der bisherigen Demenztherapie Die klinische Relevanz von Acetylcholinesterase-Inhibitoren (AChE-I) zur symptomatischen Therapie der leichten bis mäßigen Alzheimer-Demenz ist weltweit anerkannt, trotz nur mäßiger Wirksamkeit. Die Anwendung sollte bei Verträglichkeit auch im schweren Krankheitsstadium fortgeführt werden. Bei mäßiger bis schwerer Alzheimer-Demenz ist der NMDA-Rezeptor-Antagonist Memantin indiziert. Die Lewy-Körperchen-Demenz ist in der antidementiven Therapie der Alzheimer-Demenz gleichgestellt, für die Parkinson-Demenz existiert eine Indikation für Rivastigmin. Eine Veränderung der motorischen Symptome unter AChE-I ist zu beachten. Für frontotemporale oder vaskuläre Demenzen gibt es keine evidenz-basierte antidementive Therapie.

Therapie-Monitoring und Wirksamkeitsbeurteilung Der Wirksamkeitsnachweis der Demenztherapie im Einzelfall ist schwierig. Jede Demenztherapie sollte deshalb, Verträglichkeit vorausgesetzt, langfristig angelegt und regelmäßig überprüft werden.

Andere medikamentöse Therapiestrategien in der Behandlung demenzieller Erkrankungen Für Souvenaid und Ginkgo biloba als ergänzende antidementive Behandlung bei Alzheimer-Demenz gibt es Hinweise auf einen Nutzen. Andere Therapieansätze sind nicht belegt.

Zukunftsaussichten für eine krankheitsmodifizierende Therapie Die Modulation des Verlaufs von Demenzerkrankungen ist Schwerpunkt von aktuellen klinischen Studien. Anti-Amyloid- (in Phase-III-Studien) und Anti-Tau-Strategien (derzeit in Phase-II-Studien) werden intensiv verfolgt neben anderen Therapieansätzen. Statt des Demenzstadiums wird die leichte kognitive Störung bei Alzheimer-Krankheit als sinnvollste Interventionspopulation angezielt.
Carbon dioxide versus room air for colonoscopy in deeply sedated pediatric patients: a randomized controlled trial
Authors: Kresz Andrea , Mayer Benjamin , Zernickel Maria , Posovszky Carsten
Published: January 2019

Background and study aims Use of carbon dioxide (CO2) instead of room air (RA) during colonoscopy in adults revealed significantly less flatulence and abdominal pain in several studies. The objectives of this study were to investigate the effects of CO2 usage on post-interventional pain, abdominal discomfort, abdominal girth, pCO2 levels, and narcotic requirement in deeply sedated pediatric patients.

Patients and methods A total of 97 children and adolescents aged 4 years to 17 years undergoing colonoscopy were randomized to RA or CO2 in a prospective, randomized, controlled trial. Age-appropriate pain scales assessed abdominal pain as primary outcome. In addition, abdominal girth, abdominal bloating, transcutaneous pCO2, narcotic requirement to achieve deeply sedation, and post-procedural analgesic demand was analyzed in 73 patients.

Results Overall, significantly fewer patients reported bloating in the CO2 group (P = 0.0012). However, we observed only a trend to lower post-interventional pain (P = 0.15) and a lower pain score. There was no significant difference in transcutaneous pCO2 level and no adverse events occurred. Although there was no difference in the dosage of propofol and midazolam, we observed a significant increased necessity for use of synthetic opioids in the RA group to achieve optimal examination conditions (P = 0.023).

Conclusions The benefits using CO2 in colonoscopy of deeply sedated children predominate. In particular, CO2 insufflation may allow a less painful post-interventional time and it significantly reduces abdominal bloating. Moreover, with CO2, significantly less additional opioids were used. Thus, CO2 insufflation can be considered as safe in deeply sedated patients as there was no relevant pulmonary CO2 retention observed. (DRKS00013914)
A Case-control Study of Exercise and Kidney Disease: Hemodialysis and Transplantation
Authors: Silva-Filho Antonio , Azoubel Luana , Barroso Rodrigo , Carneiro Erika , Dias-Filho Carlos , Ribeiro Rachel , Garcia Alessandra , Dias Carlos , Rodrigues Bruno , Mostarda Cristiano
Published: January 2019

We aimed to analyze the effect of an exercise training program in autonomic modulation, and exercise tolerance of hemodialysis and kidney-transplanted patients. 4 groups of exercised and non-exercised patients undergoing hemodialysis and kidney-transplanted subjects had their biochemical tests, and heart rate variability evaluations analyzed. Also, sleep quality, anxiety and depression questionnaires were evaluated. Both exercised groups showed improvements in cardiovascular autonomic modulation, biochemical markers, and exercise tolerance after the exercise training program. The exercised kidney-transplanted patients group showed better improvements in cardiovascular autonomic modulation, biochemical markers, and exercise tolerance when compared to the exercised hemodialysis patients group. Both groups showed improvements in sleep quality, anxiety, and depression. The group of kidney-transplanted patients show better results in the cardiovascular autonomic modulation than subjects undergoing hemodialysis. However, the patients undergoing hemodialysis showed improvements in blood pressure, HDL, hemoglobin and phosphorus, changes not observed in the kidney-transplanted group. Exercise is beneficial for both hemodialysis and kidney-transplanted patients groups. However, exercise programs should be focused mainly in improving cardiovascular risk factors in the HD patients.
Hemiballistisch-choreatiforme Bewegungsstörung durch eine nicht-ketotische Hyperglykämie
Authors: Meyer Tareq , Dafotakis Manuel
Published: January 2019

Einleitung Eine nicht-ketotische Hyperglykämie kann über eine Affektion der Basalganglien zu einer hemiballistisch-hemichoreatischen Bewegungsstörung führen.

Anamnese Ein 68-jähriger Patient stellte sich mit einer subakut aufgetretenen und schmerzlosen hemiballistisch-choreatischen Bewegungsstörung vor.

Untersuchungen und Diagnose Eine erweiterte laborchemische und bildgebende Diagnostik konnte bei einem HbA1c von 16,4 %, negativen Ketonkörpern im Urin sowie charakteristischem MR-grafischem Nachweis eines hyperintensen Striatums in der T1-Wichtung die Diagnose einer nicht-ketotischen Hyperglykämie-induzierten Bewegungsstörung erbringen.

Therapie und Verlauf Eine antidiabetische Therapie mit Metformin, Insulin glargin und Sitagliptin sowie eine symptomatische Therapie mit 3 mg Risperidon wurde begonnen. Die Blutzuckerwerte normalisierten sich, sodass es im frühen stationären Verlauf zu einer langsamen und leichtgradigen Regredienz der Bewegungsstörung kam.

Folgerung Die genauen pathophysiologischen Mechanismen dieser Bewegungsstörung sind noch nicht voll verstanden. Bei entsprechender Klinik und passenden laborchemischen wie bildmorphologischen Befunden sollte aber immer an eine mögliche nicht-ketotische Hyperglykämie-induzierte Bewegungsstörung gedacht werden.
Antibiotikanutzung bei Menschen mit türkischem
Migrationshintergrund – Wissen, Einstellungen und Interaktion mit
ÄrztInnen und ApothekerInnen
Authors: Erdsiek Fabian , Aksakal Tugba , Özcebe Hilal , Üner Sarp , Caman Ozge Karadag , Czabanowska Katarzyna , Gershuni Olga , Westerling Ragnar , Brzoska Patrick
Published: January 2019

Ziel der Arbeit Kulturelle Aspekte der Medikamentennutzung in der
Türkei können aufgrund ausgeprägter transnationaler
Beziehungen das Nachfrageverhalten von Menschen mit türkischem
Migrationshintergrund in Deutschland beeinflussen. Über die
Antibiotikanutzung in dieser Bevölkerungsgruppe ist allerdings wenig
bekannt. Die Studie untersucht, wie sich das Nachfrageverhalten von Menschen mit
türkischem Migrationshintergrund und die Interaktion mit dem
Gesundheitssystem im Zusammenhang mit der Antibiotikanutzung gestalten, welche
Einstellungen zugrunde liegen und wie diese mit vorhandenem Hintergrundwissen
zusammenhängen.

Methodik Mit einem qualitativen Ansatz wurden Handlungslogiken und das
Verhalten von türkeistämmigen Erwachsenen in Deutschland
untersucht. Dazu wurden leitfadengestützte Fokusgruppeninterviews mit
türkeistämmigen Erwachsenen und Experteninterviews mit
HausärztInnen und ApothekerInnen durchgeführt und
inhaltsanalytisch ausgewertet.

Ergebnisse Während bei jüngeren Menschen eine positive,
aber vorsichtige Haltung gegenüber der Einnahme von Antibiotika
vorliegt, finden sich bei Älteren teilweise übersteigerte
Erwartungen an die Wirksamkeit, die auf fehlendes Faktenwissen
zurückgehen. Insgesamt nehmen die TeilnehmerInnen eine passive
Patientenrolle in der Interaktion mit HausärztInnen ein, wodurch
bestehende Informationslücken teils nicht geschlossen werden.

Schlussfolgerungen Ältere Menschen mit türkischem
Migrationshintergrund haben teils unrealistische Erwartungen an die Wirksamkeit
von Antibiotika. In Zusammenhang mit einer passiven Patientenrolle werden
Informationsbedarfe und -bedürfnisse nicht befriedigt, was die
Arzt-Patient-Beziehung belasten kann. Eine Anpassung der Kommunikation und eine
migrationssensible Informationsvermittlung sind daher notwendig.
Fertilitätsstörungen: Therapieansätze der anthroposophischen Medizin
Authors: Stammer Gabriela
Published: January 2019

In der Anthroposophischen Medizin stehen vier Behandlungselemente im Vordergrund: das ärztliche Gespräch, Arzneimittel der Anthroposophischen Medizin, nichtmedikamentöse Heilmittel wie Eurythmie oder Kunsttherapie sowie äußere Anwendungen. Dabei werden auch biographische Aspekte und das Empfindungsleben in der Therapie berücksichtigt. Damit kann die konventionelle Therapie bei Fertilitätsstörungen sinnvoll erweitert werden.

Der Artikel fokussiert das therapeutische Vorgehen bei Corpus-luteum-Schwäche, polyzystischem Ovar und Prolactinämie.
Männliche Fertilitätsstörungen mit chinesischer Medizin behandeln
Authors: Krammer-Pojer Olivia
Published: January 2019

Obwohl die Ursachen einer ausbleibenden Schwangerschaft in etwa gleich auf beide Geschlechter verteilt sind, steht meist die Frau im Fokus. Die Spermienqualität ist in den letzten 30 Jahren erheblich gesunken, woraus eine Änderung der Normwerte für Spermiogramme durch die WHO resultierte. Die Ursachen sind vielfältig, aber zu großen Teilen auch im Lebensstil begründet. Genau diese für gesunde Spermien notwendige Lebensstiloptimierung ist eine Domäne der chinesischen Medizin.
Impact of Working Experience on Image Perception and Image Evaluation Approaches in Stroke Imaging: Results of an Eye-Tracking Study
Authors: Kammerer Sara , Schülke Christoph , Leclaire Martin Dominik , Schwindt Wolfram , Velasco Gonzalez Aglae , Zoubi Tarek , Heindel Walter , Buerke Boris
Published: January 2019

Purpose Higher rates of missed pathologies, caused by a lack of professional experience or systematic search, suggest that a methodical approach to radiological analysis can be learned. Thus, the aim of this study is to investigate the efficiency of different principles of screening stroke CTs for cerebrovascular diseases between radiologists and neuroradiologists with different levels of experience in relation to professional experience.

Methods A set of anonymous CT images of 20 patients, with a suspected stroke, was individually presented to 12 radiologists with different levels of professional experience. Meanwhile, their fixation position was recorded by an eye-tracking system. For statistical analysis, the interobserver variability and accuracy of lesion detection were evaluated, taking the individual level of professional experience into account.

Results The sensitivity of the observer depends on the professional experience, also determined by a systematic observation sequence and knowledge of the course of the disease. The duration of eye fixation with inexperienced assessors was significantly longer for conspicuous findings, while experienced assessors were more likely to fix clinically relevant regions. The retention time of ocular fixation in important pathological findings did not differ significantly between those groups.

Conclusion Our results indicate that experienced radiologists are reducing the number of missed findings through a systematic approach and targeted inspection of important regions. Through raising the awareness of analyzing CT images in systematic patterns, physicians at all levels of experience seem to be able to improve their performance.

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Citation Format
Laboratory Diagnostics in Thrombophilia
Authors: Hart Christina , Linnemann Birgit
Published: January 2019

A thrombophilic disorder is a hereditary or acquired condition that increases the risk of thrombosis. The most common hereditary thrombophilias that predispose to venous thrombosis in the Caucasian population are the heterozygous forms of the factor V Leiden and prothrombin G20210A mutation that are generally detected by direct DNA genotyping. Immunologic antigen assays and chromogenic or clot-based activity assays are used to identify deficiencies in the natural coagulation inhibitors antithrombin, protein C and protein S. Because pre-analytical errors and acquired causes of low antithrombin, protein C or protein S levels are considerably more common than hereditary deficiencies, all potential conditions that may lower activity levels of the natural coagulation inhibitors (e.g. concomitant liver disease, pregnancy, anticoagulant therapy) must be considered and excluded before the diagnosis of an inhibitor deficiency can be made. To avoid misclassification, the diagnosis should not be made based on a single abnormal test result. Thus, repetitive testing when the patient is not on anticoagulant therapy is mandatory to confirm the diagnosis. Screening for antiphospholipid syndrome (APS) comprises testing for lupus anticoagulants (LAs) and the presence of IgG or IgM antibodies directed against phospholipids and phospholipid-binding proteins such as β-2-glycoprotein-I. A combination of clot-based assays has been recommended to demonstrate LA activity, whereas solid-phase immunoassays allow the detection of anti-cardiolipin and anti-β-2-glycoprotein-I antibodies. The diagnosis of APS requires the persistence of antiphospholipid antibodies for at least 12 weeks together with thrombotic and/or obstetric features of APS.