bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Extended-Spectrum Beta-Lactamases-Producing Microorganisms in Patients Admitted at KRRH, Southwestern Uganda
Authors: Andrew Baguma , Kagirita Atek , Bazira Joel
Published: February 2017

The emergence of extended-spectrum beta-lactamase- (ESBL-) producing pathogenic bacteria at Kabale Regional Referral Hospital (KRRH), located in southwestern Uganda, is of great concern: a phenomenon that worries clinicians and other healthcare workers due to the serious threat they pose to patients. This current study aimed at determining the phenotypic detection of ESBL-producing strains ofE. coli, Klebsiellasp., andProteussp. isolated from clinical specimens and their prevalence in patients admitted at KRRH. We used combined disc diffusion technique to detect and establish the presence of ESBLs-producing bacteria. Of the 100 tested bacterial isolates, 89 (89%) were identified as ESBL-producing bacteria.Klebsiellasp. predominated in the samples (46 (52%)), presenting the highest frequency of ESBLs producing followed byE. coli(39 (44%)) andProteus mirabilis(4 (4.5%)) from the combined disk diffusion.
A MapReduce Based High Performance Neural Network in Enabling Fast Stability Assessment of Power Systems
Authors: Liu Yang , Liu Youbo , Liu Junyong , Li Maozhen , Liu Tingjian , Taylor Gareth , Zuo Kunyu
Published: February 2017

Transient stability assessment is playing a vital role in modern power systems. For this purpose, machine learning techniques have been widely employed to find critical conditions and recognize transient behaviors based on massive data analysis. However, an ever increasing volume of data generated from power systems poses a number of challenges to traditional machine learning techniques, which are computationally intensive running on standalone computers. This paper presents a MapReduce based high performance neural network to enable fast stability assessment of power systems. Hadoop, which is an open‐source implementation of the MapReduce model, is first employed to parallelize the neural network. The parallel neural network is further enhanced with HaLoop to reduce the computation overhead incurred in the iteration process of the neural network. In addition, ensemble techniques are employed to accommodate the accuracy loss of the parallelized neural network in classification. The parallelized neural network is evaluated with both the IEEE 68‐node system and a real power system from the aspects of computation speedup and stability assessment.
TMEM187-IRAK1Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin
Authors: Khalifa Olfa , Balandraud Nathalie , Lambert Nathalie , Auger Isabelle , Roudier Jean , Sénéchal Audrey , Geneviève David , Picard Christophe , Lefranc Gérard , Touitou Isabelle , Mrenda Bakridine M’Madi , Benedito Cécilia , Pardoux Etienne , Gagez Anne-Laure , Pers Yves-Marie , Jorgensen Christian , Mahjoub Touhami , Apparailly Florence
Published: February 2017

Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containingTMEM187andIRAK1(rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (n=408) compared with age-matched controls (n=471) in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts. The rs1059702 C major allele was significantly associated with RA, only with French women. In the French population, the GTC haplotype displayed a protective effect against RA, while the ATC, GCC, and GTT haplotypes conferred significant risk for RA. No association for these haplotypes was found in the Tunisian population. Our results replicated for the first time the association of the three Xq28 polymorphisms with RA risk in Tunisian and French populations and suggested that RA susceptibility is associated withTMEM187-IRAK1polymorphisms in women. Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations.
Analysis on the Correlation Degree between the Driver’s Reaction Ability and Physiological Parameters
Authors: Li Shiwu , Guo Mengzhu , Wang Linhong , Chai Meng , Chen Facheng , Wei Yunong
Published: February 2017

In this paper, the correlation degree between driver’s reaction time and the physiological signal is analyzed. For this purpose, a large number of road experiments are performed using the biopac and the reaction time test systems to collect data. First, the electroencephalograph (EEG) signal is processed by using the fast Fourier and the inverse Fourier transforms. Then, the power spectrum densities (PSD) of α, β, δ, and EEG wave are calculated by Welch procedure. The average power of the power spectrum of α, β, and θ is calculated by the biopac software and two ratio formulas, (α + θ)/β and α/β, are selected to be the impact factors. After that the heart rate and the standard deviation of RR interval are calculated from the electrocardiograph (ECG) signal. Lastly, the correlation degree between the eight impact factors and the reaction time are analyzed based on the grey correlation analysis. The results demonstrate that α/β has the greatest correlation to the reaction time except EEG‐PSD. Furthermore, two mathematical models for the reaction time‐driving time and the α/β‐driving time are developed based on the Gaussian function. These mathematical models are then finally used to establish the functional relation of α/β‐the reaction time.
Gram-Charlier Processes and Applications to Option Pricing
Authors: Chateau Jean-Pierre , Dufresne Daniel
Published: February 2017

A Gram-Charlier distribution has a density that is a polynomial times a normal density. For option pricing this retains the tractability of the normal distribution while allowing nonzero skewness and excess kurtosis. Properties of the Gram-Charlier distributions are derived, leading to the definition of a process with independent Gram-Charlier increments, as well as formulas for option prices and their sensitivities. A procedure for simulating Gram-Charlier distributions and processes is given. Numerical illustrations show the effect of skewness and kurtosis on option prices.
Virtualized ANR to Manage Resources for Optimization of Neighbour Cell Lists in 5G Mobile Wireless Networks
Authors: Shin Yoonsu , Kim Songkuk
Published: February 2017

In future, more devices such as wearable devices will be connected to the networks. This will increase simultaneous handovers. The coverage of a cell will be small because a superhigh frequency used in 5G wireless networks does not propagate very far. This trend will increase the number of neighbour cell lists and it will accelerate the change of neighbour cell lists since the coverage of cells can be altered by the environment. Meanwhile, the ANR technology will be essential in 5G networks. Since the network environment in the future is not similar to the present, the strategy of ANR should also be different from the present. First, since practical neighbour cell lists in each cell are changed frequently and individually, it is necessary to optimize them frequently and individually. Second, since the neighbour cell lists in each cell are not changed similarly, it is necessary to operate ANR flexibly. To respond to these issues, we propose to use network function virtualization (NFV) for ANR. To evaluate the proposed strategies, we measured additional resource consumption and the latency of handover if neighbour cell lists are not optimized when UEs perform handover simultaneously. These experiments are conducted using Amarisoft LTE-100 Platform.
Circular RNA ciRS-7—A Promising Prognostic Biomarker and a Potential Therapeutic Target in Colorectal Cancer
Authors: Weng Wenhao , Wei Qing , Toden Shusuke , Yoshida Kazuhiro , Nagasaka Takeshi , Fujiwara Toshiyoshi , Cai Sanjun , Qin Huanlong , Ma Yanlei , Goel Ajay
Published: February 2017

Purpose: Colorectal cancer is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. As miR-7, a putative tumor-suppressor, regulates the expression of several important drivers of colorectal cancer, we analyzed the clinical significance of ciRS-7 in colorectal cancer patients.

Experimental Design: Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary colorectal cancer tissues and 44 matched normal mucosae. We subsequently confirmed its clinical relevance in an independent validation cohort (n = 165), and evaluated the effect of ciRS-7 on miR-7, and its target genes EGFR and RAF1. Functional analyses were performed in cell lines and an animal model to support clinical findings.

Results: Our data revealed that ciRS-7 was significantly upregulated in colorectal cancer tissues compared with matched normal mucosae (P = 0.0018), and its overexpression was associated with poor patient survival (P = 0.0224 and 0.0061 in the training and validation cohorts, respectively). Multivariate survival analysis revealed that ciRS-7 emerged as an independent risk factor for overall survival (P = 0.0656 and 0.0324 in the training and validation cohorts, respectively). Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes.

Conclusions: CiRS-7 is a promising prognostic biomarker in colorectal cancer patients and may serve as a therapeutic target for reducing EGFR-RAF1 activity in colorectal cancer patients. Clin Cancer Res; 23(14); 3918–28. ©2017 AACR.
The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function
Authors: Wan Lixin , Chen Ming , Cao Juxiang , Dai Xiangpeng , Yin Qing , Zhang Jinfang , Song Su-Jung , Lu Ying , Liu Jing , Inuzuka Hiroyuki , Katon Jesse M. , Berry Kelsey , Fung Jacqueline , Ng Christopher , Liu Pengda , Song Min Sup , Xue Lian , Bronson Roderick T. , Kirschner Marc W. , Cui Rutao , Pandolfi Pier Paolo , Wei Wenyi
Published: February 2017

BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APCFZR1, APCFZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APCFZR1, leading to elevation of a cohort of oncogenic APCFZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APCFZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion cooperates with AKT hyperactivation to transform primary melanocytes, whereas genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant coactivation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis.

Significance: FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APCFZR1 E3 ligase activity. Aberrancies in this newly defined signaling network might account for BRAF hyperactivation in human cancers, suggesting that targeting CYCLIN D1/CDK4, alone or in combination with BRAF/MEK inhibition, can be an effective anti-melanoma therapy. Cancer Discov; 7(4); 424–41. ©2017 AACR.

See related commentary by Zhang and Bollag, p. 356.

This article is highlighted in the In This Issue feature, p. 339
Late-Onset of Acute Severe Ulcerative Colitis: Clinical Case
Authors: Dorofeyev A.E. , Rassokhina O.A. , Dorofeyeva A.A.
Published: February 2017

Ulcerative colitis (UC) in adult age requires more careful examination because more often it turns out to be a complication related to the precancer condition. The onset of colitis in older age is predicted to follow a more aggressive clinical course and requires more frequent hospitalizations and steroids prescription in contrast to its onset in young patients. Even as this remains unclear, we present here a clinical case of late onset of acute severe UC to represent interesting clinical peculiarities and response to the therapy. Patient P., a 57-year-old male complained of 8 days of bloody diarrhea and lower abdominal pain. He reported having up to 3-5 urgent stool per day and 3-4 stool per night weight loss with dehydration. Stool culture was negative for infection, but fecal leukocytes were present. Flexible colonoscopy and biopsies were performed, which showed friable and erythematous mucosa with erosions and ulcers in a diffuse circumferential distribution from the anal verge to the cecum. There were no pseudomembranes. Histological evaluation revealed acute inflammation without architectural distortion consistent with either acute infectious colitis or new inflammatory bowel disease, favoring UC. Treatment for presumed UC is initiated with mesalazine 8 g daily: 4 g orally, 4 g per rectum and prednisone at 40 mg orally daily. After 48 h, stool frequency was 12 times per day (2 per night) with urgency, and blood was seen in stool occasionally. Intravenous steroids were prescribed - 16 mg of dexamethasone. After 48 h, stool frequency reduced to 8 per day, 1-2 per night, with traces of blood in stool and general well-being was increased. But after 14 days, the condition did not change significantly. Infliximab 5 mg/kg was administered and after the first infusion, stool frequency reduced to 4 times per day without urgency and night diarrhea. Azathioprine 100 mg per day was prescribed after steroid (prednisone) withdrawal. But after the third infusion of infliximab, the patient felt pain along the intercostal nerves along with skin redness and itching. Herpes zoster virus infection was diagnosed. Famciclovir 750 mg per day was prescribed, azathioprine was stopped, infusions of infliximab were continued and after 12 months, patient was started on a monotherapy of infliximab 1 time per 8 weeks and he had stable remission.
Combining Therapeutic Drug Monitoring with Biosimilars, a Strategy to Improve the Efficacy of Biologicals for Treating Inflammatory Bowel Diseases at an Affordable Cost
Authors: Gils Ann
Published: February 2017

Background: Biologicals provide a tight disease control but not all patients respond favourably to treatment. Some patients do not respond at all (primary non-responders), while other patients respond initially but show loss of response over time (secondary non-responders). Drug concentrations in the serum of patients can be monitored and correlated with biological, clinical or endoscopic response. Therapeutic thresholds have been defined for infliximab and adalimumab. The European Medicines Agency has approved 3 biosimilars of infliximab and new biosimilars are waiting approval. Key Messages: Distinguishing primary non-responders from patients with insufficient drug exposure during induction through drug serum concentration determination will improve drug efficacy. Current algorithms to guide treatment of patients with secondary loss of response take into account that patients with high titers of anti-drug antibodies (ADA) do not respond to dose intensification and that patients with therapeutic drug concentrations cannot be switched to biologicals within class. For patients in clinical remission, the cost of biological treatment can be decreased by dose tapering patients with supra-therapeutic concentrations and/or by switching patients with adequate drug concentrations and no formation of ADA to biosimilar, whereas efficacy can be increased by dose-intensifying patients with low or transient ADA and by switching patients with persistent ADA to biologicals within or out-off class. Conclusions: As an objective tool, therapeutic drug monitoring can identify patients who are eligible for dose tapering, intensification of treatment, cessation of treatment, switching within- or out-of-class and switching to biosimilar.
Experience with Biosimilar Infliximab (Remsima®) in Norway
Authors: Jahnsen Jørgen , Kaasen Jørgensen Kristin
Published: February 2017

Background: The first monoclonal antibody biosimilar to be used in clinical practice is the tumour necrosis factor-alpha inhibitor Remsima® (CT-P13). The drug is approved for all indications as the originator infliximab (Remicade®) although clinical efficacy has been demonstrated only in rheumatic diseases. Since the fall of 2013, Remsima® has been available in Norway and from January 2014, it has been the drug of choice when initiating biological treatment in biologics naïve patients with inflammatory bowel disease (IBD). However, many gastroenterologists have been greatly concerned about the extrapolation of indication. Switching between Remsima® and the innovator product is another issue that has been discussed. Key Messages: Good efficacy, tolerability and safety were demonstrated in a prospective observational study of IBD patients with moderate to severe disease activity. After 14 weeks of treatment there was a significant reduction in the Harvey Bradshaw index in patients with Crohns disease (CD) and reduction in the partial Mayo score and simple clinical colitis activity index in patients with ulcerative colitis. In both patient groups, there was also a significant reduction in fecal calprotectin and C-reactive protein (CRP). In another observational study, IBD patients on maintenance treatment with Remicade® were switched to Remsima®. By comparing values before and after switch, no changes in activity indices, CRP or calprotectin were observed. However, a significant increase in infliximab trough levels was shown in the CD group. No unexpected adverse events occurred after switching. Conclusions: Based on our experience in Norway, Remsima® seems to be efficacious and well tolerated in IBD. The increasing use of Remsima® in clinical practice has also contributed to significant cost savings on the health budget. Results from the NOR-SWITCH study will be available during 2016 and will hopefully contribute to answer some of the important questions that have been raised following the introduction of biosimilars as a treatment option for IBD and other immune-mediated inflammatory diseases.
Fecal Microbiota Transplantation in Inflammatory Bowel Disease
Authors: Reinisch Walter
Published: February 2017

The etiology of inflammatory bowel disease (IBD) is unknown, but it is thought to arise from an aberrant immune response to a change in colonic environment in a genetically susceptible individual. The intestinal microbiota are located at the complex interface of the epithelial barrier and are sensitive to changes in environmental factors, such as diets, drugs or smoking and signals derived from the intestinal immune system and the gut-brain axis. In patients with IBD, an imbalance in the structural and/or functional configuration of the intestinal microbiota leading to the disruption of the host-microorganism homeostasis (dysbiosis) has been reproducibly reported. As animal models of IBD require gut bacteria to induce inflammation, it is hypothesized that the dysbiosis observed in patients is not only a surrogate of changes at the intestinal barrier but also a potential cause or at least enhancer of the mucosal inflammatory process. That burgeoning notion has stimulated thoughts to modify the intestinal microbiota and rekindled interest in previous work on the efficacy of antibiotics in patients with IBD. The feasibility and tremendous success of fecal microbiota transplantation (FMT) to treat antibiotic resistant Clostridium difficile has finally paved the way to embark into the unchartered territory of IBD using FMT. Different routes and number of administrations, choices of donors, disease status and permitted therapies might have contributed to mixed results, particularly from the so far published randomized controlled trials. However, microbiome analysis suggests that a durable transplantation of donor bacteria to the host appears feasible and might be associated with a higher likelihood of response. On the other hand, this raises the concern of transplanting not only anti-inflammatory active bacteria and their products, but also not-yet-known dispositions for other diseases including cancer. Attempts are being made to better characterize those components of the microbiome of healthy individuals, which might mediate anti-inflammatory functions and assemble ‘synthetic stools' for more standardized treatment approaches.
Applicability of Cone Beam Computed Tomography to the Assessment of the Vocal Tract before and after Vocal Exercises in Normal Subjects
Authors: Garcia Elisângela Zacanti , Yamashita Hélio Kiitiro , Garcia Davi Sousa , Padovani Marina Martins Pereira , Azevedo Renata Rangel , Chiari Brasília Maria
Published: February 2017

Background/Aims: Cone beam computed tomography (CBCT), which represents an alternative to traditional computed tomography and magnetic resonance imaging, may be a useful instrument to study vocal tract physiology related to vocal exercises. This study aims to evaluate the applicability of CBCT to the assessment of variations in the vocal tract of healthy individuals before and after vocal exercises. Methods: Voice recordings and CBCT images before and after vocal exercises performed by 3 speech-language pathologists without vocal complaints were collected and compared. Each participant performed 1 type of exercise, i.e., Finnish resonance tube technique, prolonged consonant “b” technique, or chewing technique. The analysis consisted of an acoustic analysis and tomographic imaging. Results: Modifications of the vocal tract settings following vocal exercises were properly detected by CBCT, and changes in the acoustic parameters were, for the most part, compatible with the variations detected in image measurements. Conclusion: CBCT was shown to be capable of properly assessing the changes in vocal tract settings promoted by vocal exercises.
Appropriate Follow-Up Strategies for Gastrointestinal Stromal Tumor Patients Based on the Analysis of Recurrent Interval and Patterns
Authors: Wada Noriko , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Masuzawa Toru , Nakatsuka Rie , Kawada Junji , Nishida Toshirou , Kimura Yutaka , Tanaka Kouji , Miyazaki Yasuhiro , Makino Tomoki , Yamasaki Makoto , Takiguchi Shuji , Mori Masaki , Doki Yuichiro
Published: February 2017

Background/Aims: Previous studies have proposed risk classifications for patients with gastrointestinal stromal tumor (GIST) after resection and have contributed to the prediction of its prognosis. However, optimal postoperative surveillance has not yet been established. Methods: We retrospectively analyzed data from 115 GIST patients who experienced recurrence after complete resection. The relationships between clinicopathological characteristics and the first recurrence sites, or time to recurrence (TTR), were investigated. We also compared the characteristics between 2 subgroups based on a TTR of ≤5 or >5 years. Results: The first recurrence occurred in the abdomen in 114 of 115 patients (99.1%); one case of esophageal GIST recurred in the lung. Gastric and small intestinal GISTs recurred most frequently in the liver or peritoneum, while the most common recurrences of colorectal GISTs were found to be local. Fourteen patients (12.2%) experienced recurrence after >5 years. Smaller tumors and those categorized as lower risk were significantly more frequent in the TTR >5 years group than in the TTR ≤5 years group. In the TTR >5 years group, local recurrence was the most frequent type of recurrence (42.9%). Conclusion: Based on abdominal examination, postoperative surveillance after complete resection for primary GISTs may be recommended for >5 years.
Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes
Authors: Yang Shiying , Zhou Bin , Xu Wei , Xue Fangfang , Nisar Muhammad Farrukh , Bian Chunxiang , Huang Xiao , Yang Li , Zhang Yiguo , Bartsch Jörg W. , Zhong Julia Li
Published: February 2017

Background: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. Objective: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. Methods: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. Results: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1. Conclusions: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.
Es bleibt unklar, ob IVB den Blutfluss in der AO und der ACM spezifisch beeinflusst
Authors: Lorenz Birgit
Published: February 2017

Ziel: Beurteilung der Auswirkung einer einmaligen intravitrealen Injektion mit Bevacizumab (IVB) auf verschiedene Parameter des Blutflusses in der Arteria ophthalmica (AO) und Arteria cerebri media (ACM) bei Säuglingen mit Retinopathia praematurorum (RPM). Material und Methoden: In diese prospektive, interventionelle Studie wurden 15 Säuglinge mit RPM eingeschlossen, die mit IVB behandelt wurden. Untersucht wurden die systolische Spitzengeschwindigkeit (PSV), die enddiastolische Geschwindigkeit, die mittlere Geschwindigkeit (MV) und der Resistivitätsindex, gemessen mittels Pulswellen-Dopplersonographie (Philips En Visor C, Amsterdam, Niederlande) in der AO und ACM vor der Injektion mit IVB sowie einen Tag, eine Woche und einen Monat nach der IVB-Injektion. Ergebnisse: Die gemessenen PSV-AO-, MV-AO- und PSV-ACM-Werte zeigten signifikante Veränderungen nach der IVB-Behandlung (p = 0,01, p = 0,02, bzw. p = 0,02). Die PSV-AO-Werte nach einer Woche und einem Monat waren signifikant niedriger als der PSV-AO-Ausgangswert vor der Behandlung (p = 0,03, bzw. p = 0,01). Der MV-AO-Wert war einen Monat nach der IVB-Behandlung signifikant niedriger als der Ausgangswert (p = 0,03). Der PSV-ACM-Wert zeigte einen signifikanten Rückgang einen Tag nach der Injektion (p = 0,03). Schlussfolgerungen: Die Studie belegt, dass IVB bei Säuglingen mit RPM signifikante Veränderungen bei Blutfluss-Parametern der AO und ACM bewirkt, wie die Dopplersonographie zeigt.
Infliximab Biosimilar (Remsima™) in Therapy of Inflammatory Bowel Diseases Patients: Experience from One Tertiary Inflammatory Bowel Diseases Centre
Authors: Kolar M. , Duricova D. , Bortlik M. , Hruba V. , Machkova N. , Mitrova K. , Malickova K. , Lukas Jr. M. , Lukas Milan
Published: February 2017

Background: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. Methods: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. Results: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. Conclusion: Switching of IBD patients from original to biosimilar IFX is effective and safe.
Bei Patienten mit Immunsuppression sollte bei Raumforderungen der Tränendrüse frühzeitig an eine opportunistische Neoplasie gedacht werden
Authors: Bertelmann Eckart
Published: February 2017

Ziel: Beschreibung der ophthalmologischen und histopathologischen Merkmale einer Frau mit granulomatösem variablem Immundefekt (common variable immunodeficiency, CVID), die sich wegen einer Schwellung des Oberlids vorstellte. Maßnahmen: Bei der Patientin wurde eine Biopsie des Oberlids und der palpebralen Tränendrüse rechts durchgeführt; die Bildgebung zeigte eine linksseitige nasopharyngeale Raumforderung, mehrere Lymphknoten im Mediastinum, bilaterale pulmonale Noduli und einen peritonealen Nodulus in der rechten Fossa iliaca. Die Schwellung des rechten Oberlids nahm zu und wurde erneut biopsiert. Ergebnisse: Die erste Oberlid-Biopsie ergab ein diffuses großzelliges B-Zell-Lymphom (DLBCL); die Diagnose wurde durch klonales IgH-Gen-Rearrangement mittels PCR gesichert. Im Hinblick auf die nasopharyngeale Raumforderung und Lymphknoten wurde klinisch der Verdacht auf DLBCL erhoben. Die Biopsie der nasopharyngealen Raumforderung ergab jedoch ein Kaposi-Sarkom (KS). Die zweite Biopsie des Oberlids und der palpebralen Tränendrüse rechts ergab KS ohne Hinweise auf DLBCL. Schlussfolgerung: Dies ist der erste dokumentierte Fall eines periokulären/orbitalen metachronen DLBCL und KS bei einem Patienten mit granulomatösem CVID. Wir diskutieren die Rolle der fluktuierenden Immunität bei CVID, um die spontane Regression des DLBCL und das variierende klinische Bild zu erklären.
Long-Term Ultraviolet A Eye Irradiation Causes Retina Denaturation in Mice
Authors: Hiramoto Keiichi , Yamate Yurika , Sato Eisuke F.
Published: February 2017

Background: Long-term ultraviolet (UV) A eye irradiation in mice initiates the induction of photoaging. However, the changes in the eye due to long-term exposure to UVA radiation are still unclear. Methods: Male C57BL/6j (control) and inducible nitric oxide synthase knockout (iNOS-/-) mice were used in this study. The eyes of the mice were locally exposed to UVA radiation for 12 months. Results: The expression of iNOS, matrix metalloproteinase-2 (MMP-2), MMP-9, vascular endothelial growth factor, β-amyloid, and macrophages in the retina all increased after UVA irradiation. Furthermore, in the iNOS-/- mice, no retinal changes were induced by UVA eye irradiation. Conclusions: These results indicated that long-term UVA eye irradiation led to iNOS-induced denaturation of the retina; however, further studies are needed to confirm these findings.
Intraoperative Radiotherapy of Breast Cancer and Its Biological Effects
Authors: Piotrowski Igor , Kulcenty Katarzyna , Wichtowski Mateusz , Murawa Dawid , Suchorska Wiktoria
Published: February 2017

Conservative breast cancer surgery followed by radiation therapy is the standard treatment for this type of cancer. Numerous studies demonstrate that 90% of local recurrences after traditional surgery occur in the same quadrant as the primary cancer. The published data suggest that the wound healing process after surgery alters the area surrounding the original tumor and the modified microenvironment is more favorable for the tumor to recur. The majority of metastases within scar initiated much research, and the consequences of these studies led to clinical trials aimed at assessing whether localized radiotherapy, such as intraoperative radiotherapy (IORT), would be more effective in inhibiting formation of local recurrence than the standard postoperative whole breast radiotherapy. IORT involves irradiation of diseased tissue directly during surgery. The rationale for this approach is the fact that the increase in the radiation dose increases local tumor control, which is the primary goal of radiation therapy. The biological basis of this process are still not thoroughly understood. Gaining new knowledge about the recurrence formation at the molecular level could serve as a starting point for further analysis and to create an opportunity to identify new targets of therapy, and possibly new therapeutic agents.
Treatment Options in Oligometastatic Disease: Stereotactic Body Radiation Therapy - Focus on Colorectal Cancer
Authors: Wild Aaron T. , Yamada Yoshiya
Published: February 2017

Background: Improvements in systemic therapy for metastatic colorectal cancer (CRC) have markedly extended survival, rendering local control of metastases to critical organs of increasing importance, especially in the oligometastatic setting where the disease may not yet have acquired the ability to widely disseminate. While surgical resection remains the gold standard for oligometastases in many organs, stereotactic body radiation therapy (SBRT) presents a non-invasive alternative for achieving local control. Methods: A literature review was performed to identify and summarize the findings of key prospective and retrospective studies that have shaped the field of SBRT for oligometastases to the lung, liver, and spine with a focus on oligometastases from CRC in particular. Results: Modern dose-escalated SBRT regimens can achieve 1-year local control rates of 77-100%, 90-100%, and 81-95% for oligometastases involving the lung, liver, and spine, respectively. Rates of grade 3 or greater toxicity with contemporary SBRT techniques are consistently low at <10% in the lung, <5% in the liver, and <2%/8% for neurologic/non-neurologic toxicity in the spine, respectively. Conclusion: SBRT appears safe and effective for treating oligometastases involving the lung, liver, and spine. Randomized trials comparing SBRT to surgical resection and other local therapeutic modalities for the treatment of CRC oligometastases bear consideration.
pH Response and Tooth Surface Solubility at the Tooth/Bacteria Interface
Authors: Mayanagi Gen , Igarashi Koei , Washio Jumpei , Takahashi Nobuhiro
Published: February 2017

Evaluating the physiochemical processes at the tooth surface/bacteria interface is important for elucidating the etiology of dental caries. This study aimed to compare the mineral solubility and protein degradation of coronal enamel (CE) and root dentin (RD), and investigate the involvement of dissolved components in bacteria-induced pH changes using a model of tooth/bacteria interface. An experimental apparatus forming a well was made of polymethyl methacrylate, and a bovine tooth (CE or RD) specimen was fixed at the bottom of the well. A miniature pH electrode was placed on the tooth, and Streptococcus mutans NCTC 10449 cells, grown in 0.5% glucose-containing complex medium, were packed into the well. The pH at the tooth/S. mutans interface was monitored continuously for 120 min after the addition of 0.5% glucose at 37°C. S. mutans cells were recovered from the wells, and the amounts of lactate and calcium were measured using a portable lactate meter and a fluorescent dye, respectively. Proteolytic activity was also evaluated fluorometrically. The pH of the RD/S. mutans interface was significantly higher than that of the CE/S. mutans interface (30 min: 6.37 ± 0.12 vs. 6.18 ± 0.11, 60 min: 6.08 ± 0.14 vs. 5.66 ± 0.27, 90 min: 5.49 ± 0.24 vs. 5.14 ± 0.22, p < 0.05). Greater amounts of calcium were dissolved from RD (3.19 ± 0.74 µg/mL) than from CE (1.84 ± 0.68 µg/mL; p < 0.05), while similar amounts of lactate were produced. Proteolytic activity was not detected at any of the interfaces. These results indicate that RD is more soluble to bacteria-induced acidification than CE. This method can contribute to the evaluation and development of caries-preventive materials.
Photometric Determination of Ammonium and Phosphate in Seawater Medium Using a Microplate Reader
Authors: Ruppersberg Hanna S. , Goebel Maren R. , Kleinert Svea I. , Wünsch Daniel , Trautwein Kathleen , Rabus Ralf
Published: February 2017

To more efficiently process the large sample numbers for quantitative determination of ammonium (NH4+) and phosphate (orthophosphate, PO43-) generated during comprehensive growth experiments with the marine Roseobacter group member Phaeobacter inhibens DSM 17395, specific colorimetric assays employing a microplate reader (MPR) were established. The NH4+ assay is based on the reaction of NH4+ with hypochlorite and salicylate, yielding a limit of detection of 14 µM, a limit of quantitation of 36 µM, and a linear range for quantitative determination up to 200 µM. The PO43-assay is based on the complex formation of PO43- with ammonium molybdate in the presence of ascorbate and zinc acetate, yielding a limit of detection of 13 µM, a limit of quantitation of 50 µM, and a linear range for quantitative determination up to 1 mM. Both MPR-based assays allowed for fast (significantly lower than 1 h) analysis of 21 samples plus standards for calibration (all measured in triplicates) and showed only low variation across a large collection of biological samples.
Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4
Authors: Abad Soraya , Vega Almudena , Hernández Eduardo , Mérida Evangelina , de Sequera Patricia , Albalate Marta , Macías Nicolás , Milla Monica , López-Gómez Juan M.
Published: February 2017

Background: Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. Methods: This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. Results: Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. Conclusion: A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.
Adenine Rich Diet Is Not a Surrogate of 5/6 Nephrectomy in Rabbits
Authors: Florens Nans , Lemoine Sandrine , Pelletier Caroline C. , Rabeyrin Maud , Juillard Laurent , Soulage Christophe O.
Published: February 2017

Background: Animal models are important tools needed to understand the mechanisms underlying the progression of renal disease and to implement new therapeutic approaches. A non-surgical model of chronic kidney disease (CKD) developed by chemical nephrectomy using an adenine-enriched diet has been shown to be a robust model to induce kidney failure in mice and rats. The purpose of this study was to implement an adenine diet to induce CKD in rabbits. Methods: Male New Zealand rabbits were fed for 4 weeks with a diet containing 0.75% (w/w) adenine, and renal function was assessed by measuring plasma urea and creatinine concentrations. The glomerular filtration rate (GFR) was measured using the plasmatic clearance of Iohexol. Kidney histology was performed with haematoxylin erythrosine saffron and Sirius red staining. Results: In contrast to what was observed in rodents, adenine diet failed to induce kidney failure in rabbits as is evident in the plasma concentrations of creatinine and urea and the direct measurement of GFR or histopathological studies. Conclusion: Adenine diet is not a surrogate of subtotal nephrectomy to induce kidney failure in rabbits. Several interspecies differences in metabolism and renal physiology could account for this observation.
The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality
Authors: Langsford David , Tang Mila , Cheikh Hassan Hicham I. , Djurdjev Ognjenka , Sood Manish M. , Levin Adeera
Published: February 2017

Background: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. Methods: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). Results: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). Conclusions: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.
Using Anchoring Vignettes in the Evaluation of Breast Cancer Survivors' Quality of Life
Authors: Hinz Andreas
Published: February 2017

Background: Breast cancer survivors often rate their general health as good even though they experience detriments in functioning and multiple symptoms. The hypothesis of this study is that breast cancer survivors changed their frames of reference for evaluating their own health. Methods: A sample of 308 breast cancer survivors were asked to assess their state of health on a 0-100 scale. In addition, 2 vignettes (fictional persons suffering from various health complaints) were designed. The cancer survivors were asked to assess the health of the characters in these vignettes as well. A sample of the general population (n = 639) served as controls. Results: There were only marginal differences between the cancer survivors (M = 65.8) and the controls (M = 65.5) in how they assessed their own state of health. However, the cancer survivors rated the vignette character with physical problems as being significantly healthier compared to the general population (effect size: d = 0.55). The group differences in the assessment of the vignette character with mental problems was markedly lower (d = 0.12). Conclusions: It is not sufficient to assess the general self-assessed health state of cancer survivors. Anchoring vignettes are a promising tool for use in correcting for response shift effects.
Clinical Features and Outcomes of a Racially Diverse Population with Fibrillary Glomerulonephritis
Authors: Payan Schober Fernanda , Jobson Meghan A. , Poulton Caroline J. , Singh Harsharan K. , Nickeleit Volker , Falk Ronald J. , Jennette J. Charles , Nachman Patrick H. , Pendergraft III William F.
Published: February 2017

Background: Fibrillary glomerulonephritis is characterized by randomly arranged fibrils, approximately 20 nm in diameter by electron microscopy. Patients present with proteinuria, hematuria and kidney insufficiency, and about half of the reported patients progress to end-stage kidney disease within 4 years. The dependence of patient characteristics and outcomes on race has not been explored. In this study, we describe a cohort of patients with fibrillary glomerulonephritis and compare their clinical characteristics and outcomes with those of patients previously described. Methods: The University of North Carolina (UNC) Nephropathology Database was used to retrospectively identify patients diagnosed with fibrillary glomerulonephritis between 1985 and 2015. Of these patients, those treated at UNC were selected. Their demographic and clinical characteristics - including signs and symptoms, comorbidities, laboratory values, treatments and outcomes - were compared with those of patients described earlier. Results: Among the 287 patients identified, 42 were treated at the UNC Kidney Center. When compared to earlier cohorts, a higher frequency of black race, hepatitis C virus (HCV) infection and use of hemodialysis were noted in both black and HCV-positive patients. Autoimmune diseases, infections and malignancies were frequently observed, present in over half of all cases. Conclusion: According to this study, fibrillary glomerulonephritis represents a secondary glomerular disease process (associated with autoimmune disease, infection or malignancy) in many cases and hence screening is essential. As the screening for comorbidities increased over time, more underlying causes were identified. We noted a high frequency of HCV among black patients, suggesting a possible causative association. Treatment of underlying disease is essential for patients for the best outcome.