bluuebunny/crossref_metadata_2025 huggingface dataset:
Tick-Borne Encephalitis Virus Habitats in North East Germany: Reemergence of TBEV in Ticks after 15 Years of Inactivity
Authors: Frimmel Silvius , Krienke Anja , Riebold Diana , Loebermann Micha , Littmann Martina , Fiedler Karin , Klaus Christine , Süss Jochen , Reisinger Emil Christian
Published: July 2014

The incidence of tick-borne encephalitis has risen in Europe since 1990 and the tick-borne encephalitis virus (TBEV) has been documented to be spreading into regions where it was not previously endemic. In Mecklenburg-West Pomerania, a federal state in Northern Germany, TBEV was not detectable in over 16,000 collected ticks between 1992 and 2004. Until 2004, the last human case of TBE in the region was reported in 1985. Following the occurrence of three autochthonous human cases of TBE after 2004, however, we collected ticks from the areas in which the infections were contracted. To increase the chance of detecting TBEV-RNA, some of the ticks were fed on mice. Using nested RT-PCR, we were able to confirm the presence of TBEV in ticks for the first time after 15 years. A phylogenetic analysis revealed a close relationship between the sequences we obtained and a TBEV sequence from Mecklenburg-East Pomerania published in 1992 and pointed to the reemergence of a natural focus of TBEV after years of low activity. Our results imply that natural foci of TBEV may either persist at low levels of activity for years or reemerge through the agency of migrating birds.
Physicochemical Characteristics of Bone Substitutes Used in Oral Surgery in Comparison to Autogenous Bone
Authors: Berberi Antoine , Samarani Antoine , Nader Nabih , Noujeim Ziad , Dagher Maroun , Kanj Wasfi , Mearawi Rita , Salemeh Ziad , Badran Bassam
Published: July 2014

Bone substitutes used in oral surgery include allografts, xenografts, and synthetic materials that are frequently used to compensate bone loss or to reinforce repaired bone, but little is currently known about their physicochemical characteristics. The aim of this study was to evaluate a number of physical and chemical properties in a variety of granulated mineral-based biomaterials used in dentistry and to compare them with those of autogenous bone. Autogenous bone and eight commercial biomaterials of human, bovine, and synthetic origins were studied by high-resolution X-ray diffraction, atomic absorption spectrometry, and laser diffraction to determine their chemical composition, calcium release concentration, crystallinity, and granulation size. The highest calcium release concentration was 24. 94 mg/g for Puros and the lowest one was 2.83 mg/g for Ingeniosβ-TCP compared to 20.15 mg/g for natural bone. The range of particles sizes, in terms of median size D50, varied between 1.32 μm for BioOss and 902.41 μm for OsteoSponge, compared to 282.1 μm for natural bone. All samples displayed a similar hexagonal shape as bone, except Ingeniosβ-TCP, Macrobone, and OsteoSponge, which showed rhomboid and triclinic shapes, respectively. Commercial bone substitutes significantly differ in terms of calcium concentration, particle size, and crystallinity, which may affect theirin vivoperformance.
Examination of the Behavior of Gravity Quay Wall against Liquefaction under the Effect of Wall Width and Soil Improvement
Authors: Firoozi Ali Akbar , Taha Mohd Raihan , Mir Moammad Hosseini S. M. , Firoozi Ali Asghar
Published: July 2014

Deformation of quay walls is one of the main sources of damage to port facility while liquefaction of backfill and base soil of the wall are the main reasons for failures of quay walls. During earthquakes, the most susceptible materials for liquefaction in seashore regions are loose saturated sand. In this study, effects of enhancing the wall width and the soil improvement on the behavior of gravity quay walls are examined in order to obtain the optimum improved region. The FLAC 2D software was used for analyzing and modeling progressed models of soil and loading under difference conditions. Also, the behavior of liquefiable soil is simulated by the use of “Finn” constitutive model in the analysis models. The “Finn” constitutive model is especially created to determine liquefaction phenomena and excess pore pressure generation.
Arsenic Modulates Posttranslational S-Nitrosylation and Translational Proteome in Keratinocytes
Authors: Huang Bin , Chiang Kuo-Hao , Yu Hsin-Su , Chen Ying-Lun , You Huey-Ling , Liao Wei-Ting
Published: July 2014

Arsenic is a class I human carcinogen (such as inducing skin cancer) by its prominent chemical interaction with protein thio (-SH) group. Therefore, arsenic may compromise protein S-nitrosylation by competing the -SH binding activity. In the present study, we aimed to understand the influence of arsenic on protein S-nitrosylation and the following proteomic changes. By using primary human skin keratinocyte, we found that arsenic treatment decreased the level of protein S-nitrosylation. This was coincident to the decent expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). By using LC-MS/MS, around twenty S-nitrosoproteins were detected in the biotin-switched eluent. With the interest that arsenic not only regulates posttranslational S-nitrosylation but also separately affects protein’s translation expression, we performed two-dimensional gel electrophoresis and found that 8 proteins were significantly decreased during arsenic treatment. Whether these decreased proteins are the consequence of protein S-nitrosylation will be further investigated. Taken together, these results provide a finding that arsenic can deplete the binding activity of NO and therefore reduce protein S-nitrosylation.
An Energy-Efficient Collaborative Target Tracking Framework in Distributed Wireless Sensor Networks
Authors: Shang Lin , Zhao Kang , Cai Zhengguo , Gao Dan , Hu Maolin
Published: July 2014

Energy consumption and tracking accuracy are two significant issues for collaborative tracking in distributed wireless sensor networks (DWSNs). To obtain a benefit from those issues, most of the recent work tends to reduce the spatial redundancy, while ignoring utilizing the attribute of time redundancy. In this paper, a novel energy-efficient framework of collaborative signal and information fusion is proposed for acoustic target tracking. The proposed fusion algorithm is based on neural network aggregation model and Gaussian particle filtering (GPF) estimation. And the neural network based aggregation (NNBA) can reduce spatial and time redundancy. Furthermore, a fresh cluster head (CH) selection method demanding less task handover is also presented to decrease energy consumption. The analyzed framework coupled with simulations demonstrates its excellent performance in tracking accuracy and energy consumption.
Donor Heart Utilization following Cardiopulmonary Arrest and Resuscitation: Influence of Donor Characteristics and Wait Times in Transplant Regions
Authors: Quader Mohammed , Wolfe Luke , Katlaps Gundars , Kasirajan Vigneshwar
Published: July 2014

Background. Procurement of hearts from cardiopulmonary arrest and resuscitated (CPR) donors for transplantation is suboptimal. We studied the influences of donor factors and regional wait times on CPR donor heart utilization.Methods. From UNOS database (1998 to 2012), we identified 44,744 heart donors, of which 4,964 (11%) received CPR. Based on procurement of heart for transplantation, CPR donors were divided into hearts procured (HP) and hearts not procured (HNP) groups. Logistic regression analysis was used to identify predictors of heart procurement.Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HP group. Donor characteristics that favored heart procurement include younger age (25.5 ± 15 yrs versus 39 ± 18 yrs,P≤0.0001), male gender (34% versus 23%,P≤0.0001), shorter CPR duration (<15 min versus >30 min,P≤0.0001), and head trauma (60% versus 15%). Among the 11 UNOS regions, the highest procurement was in Region 1 (37%) and the lowest in Region 3 (24%). Regional transplant volumes and median waiting times did not influence heart procurement rates.Conclusions. Only 28.8% of CPR donor hearts were procured for transplantation. Factors favoring heart procurement include younger age, male gender, short CPR duration, and traumatic head injury. Heart procurement varied by region but not by transplant volumes or wait times.
Using Adhesive Glue to Repair First Degree Perineal Tears: A Prospective Randomized Controlled Trial
Authors: Feigenberg Tomer , Maor-Sagie Esther , Zivi Einat , Abu-Dia Mushira , Ben-Meir Assaf , Sela Hen Y. , Ezra Yossef
Published: July 2014

Our objective was to evaluate the effectiveness of adhesive glue in repairing first degree perineal tears. We conducted a noninferiority prospective, randomized, controlled trial comparing adhesive glue with traditional suturing. Each case was evaluated immediately after birth and after the puerperium. The two-samplet-test and the Mann-Whitney nonparametric test were applied to compare quantitative variables between the treatment groups. The chi-squared test and Fisher's exact test were used to assess the association between qualitative variables. A total of 102 women participated, 28 in the suture arm and 74 in the adhesive glue arm. While cosmetic and functional results of adhesive glue use were not inferior to suturing, the use of adhesive glue was associated with a shorter procedure, less need for local anesthetic, less pain, and greater satisfaction. Our results suggest a novel approach for the repair of common postpartum first degree lacerations. The use of adhesive glue achieves cosmetic and functional results equal to traditional suturing and offers some immediate advantages for the patient. While further clinical trials are needed to validate our results, it is important to inform obstetrician of the possible use of adhesive glue in these very common clinical scenarios. This trial is registered withNCT00746707.
Dealing with Nonregular Shapes Packing
Authors: Júnior Bonfim Amaro , Pinheiro Plácido Rogério , Saraiva Rommel Dias , Pinheiro Pedro Gabriel Calíope Dantas
Published: July 2014

This paper addresses the irregular strip packing problem, a particular two‐dimensional cutting and packing problem in which convex/nonconvex shapes (polygons) have to be packed onto a single rectangular object. We propose an approach that prescribes the integration of a metaheuristic engine (i.e., genetic algorithm) and a placement rule (i.e., greedy bottom‐left). Moreover, a shrinking algorithm is encapsulated into the metaheuristic engine to improve good quality solutions. To accomplish this task, we propose a no‐fit polygon based heuristic that shifts polygons closer to each other. Computational experiments performed on standard benchmark problems, as well as practical case studies developed in the ambit of a large textile industry, are also reported and discussed here in order to testify the potentialities of proposed approach.
Proposal of a Planar Directional UWB Antenna for Any Desired Operational Bandwidth
Authors: Peyrot-Solís Marco A. , Galvan-Tejada Giselle M. , Jardon-Aguilar Hildeberto
Published: July 2014

A novel planar directional UWB antenna is proposed. The antenna design evolves from an oblique elliptic cone antenna by applying the planar-solid correspondence to two axes. Through a simple equation, this antenna can be designed, to operate at a specific lower cutoff frequency with a bandwidth larger than 10 GHz for a reflection coefficient magnitude lower than −10 dB. This characteristic provides the antenna with a good versatility. The directional radiation pattern has an average gain of 6 dBi.
Corneal Collagen Cross-Linking with and without Epithelial Removal: A Contralateral Study with 0.5% Hypotonic Riboflavin Solution
Authors: Stojanovic Aleksandar , Zhou Wen , Utheim Tor Paaske
Published: July 2014

Purpose. Our main purpose was to compare safety and efficacy in the treatment of progressive keratoconus with “epithelium-on” and “epithelium-off” corneal collagen cross-linking (CXL). Our secondary purpose was to evaluate efficacy of CXL when hypotonic 0.5% riboflavin is used as photosensitizer.Methods. One eye of 20 patients with bilateral progressive keratoconus was randomly treated for “epithelium-on” CXL (group 1) while the fellow eye underwent “epithelium-off” CXL (group 2). Hypotonic 0.5% riboflavin was used in both groups. Visual acuity, refraction, corneal topography, and wavefront aberrometry were evaluated at baseline and after 1, 6, and 12 months. Specular microscopy was performed on 10 patients preoperatively and after 12 months. Postoperative pain was evaluated using a patient questionnaire.Results. Uncorrected and corrected distance visual acuity improved significantly in both groups. Refraction, topography, and aberrometry showed nonsignificant changes from the preoperative status throughout the 12-month follow-up in both groups. Moreover, the outcomes between the groups were comparable at all follow-up points. Endothelial cell-count was stable. Postoperative pain length was shorter in group 1P<0.001.Conclusion. “Epithelium-on” and “epithelium-off” CXL using hypotonic 0.5% riboflavin were equally safe and effective in stabilization of keratoconus. Topography and aberrometry outcomes in both groups failed to show any significant improvements. This study is registered at ClinicalTrials.gov:NCT01181219.
Changes in Antioxidant Enzyme Activity and Transcript Levels of Related Genes inLimonium sinenseKuntze Seedlings under NaCl Stress
Authors: Zhang Xia , Yin HaiBo , Chen ShiHua , He Jun , Guo ShanLi
Published: July 2014

The halophyteLimonium sinenseKuntze is used in traditional Chinese medicine for clearing heat and for detoxification. To examine the detoxification and salt-tolerance mechanisms of this plant, we analyzed antioxidant enzyme activities and transcript levels of genes encoding antioxidant enzymes inL. sinenseseedlings under salt stress (500 mmol/L NaCl). Catalase showed the largest increase in activity, peaking on day 4 of the 7-day NaCl treatment. Peroxidase and superoxide dismutase activities also increased, peaking on days 2 and 3 of the NaCl treatment, respectively. The activities of antioxidant enzymes decreased as the duration of the NaCl treatment extended. The transcript levels of genes encoding antioxidant enzymes were upregulated under NaCl stress. The peak in theLsCATtranscript level was earlier than the peaks inLsAPXandLsGPXtranscript levels. The malondialdehyde content only slightly increased inL. sinenseseedlings under NaCl stress. This was indicative of a low level of lipid peroxidation, consistent with the increased antioxidant enzyme activities and gene transcript levels. These results show that, under NaCl stress, the antioxidant system ofL. sinenseis activated and effectively scavenges reactive oxygen species. This reduces oxidative damage and allows the plant to maintain growth under NaCl stress.
Surgical Management of Mandibular Central Incisors with Dumbbell Shaped Periapical Lesion: A Case Report
Authors: Garlapati Roopadevi , Venigalla Bhuvan Shome , Patil Jayaprakash D. , Jayaprakash Thumu , Chaitanya C. H. Krishna , Kalluru Rama S.
Published: July 2014

Dental traumatic injuries may affect the teeth and alveolar bone directly or indirectly. Pulpal necrosis and chronic and apical periodontitis with cystic changes are the most common sequelae of the dental traumatic injuries, if the teeth are not treated immediately. This case report focuses on the conventional and surgical management of mandibular central incisors. A twenty-four-year-old male patient presented with pain in the mandibular central incisors. Radiographic examination revealed mandibular central incisors with dumbbell shaped periapical lesion. After root canal treatment, parendodontic surgery was performed for mandibular central incisors. After one-year recall examination, the teeth were asymptomatic and periapical lesion had healed.
Effect of Intra-Articular Hyaluronic Injection on Postural Stability and Risk of Fall in Patients with Bilateral Knee Osteoarthritis
Authors: Khalaj Nafiseh , Abu Osman Noor Azuan , Mokhtar Abdul Halim , George John , Wan Abas Wan Abu Bakar
Published: July 2014

Knee osteoarthritis is a common cause of disability which influences the quality of life. It is associated with impaired knee joint proprioception, which affects postural stability. Postural stability is critical for mobility and physical activities. Different types of treatment including nonsurgical and surgical are used for knee osteoarthritis. Hyaluronic acid injection is a nonsurgical popular treatment used worldwide. The aim of this study was to demonstrate the effect of hyaluronic acid injections on postural stability in individuals with bilateral knee osteoarthritis. Fifty patients aged between 50 and 70 years with mild and moderate bilateral knee osteoarthritis participated in our study. They were categorized into treatment(n=25)and control(n=25)groups. The treatment group received five weekly hyaluronic acid injections for both knees, whereas the control group did not receive any treatment. Postural stability and fall risk were assessed using the Biodex Stability System and clinical “Timed Up and Go” test. All the participants completed the study. The treatment group showed significant decrease in postural stability and fall risk scores after five hyaluronic acid injections. In contrast, the control group showed significant increase. This study illustrated that five intra-articular hyaluronic acid injections could significantly improve postural stability and fall risk in bilateral knee osteoarthritis patients. This trial is registered with:NCT02063373.
Upper Limb Posture Estimation in Robotic and Virtual Reality-Based Rehabilitation
Authors: Cortés Camilo , Ardanza Aitor , Molina-Rueda F. , Cuesta-Gómez A. , Unzueta Luis , Epelde Gorka , Ruiz Oscar E. , De Mauro Alessandro , Florez Julian
Published: July 2014

New motor rehabilitation therapies include virtual reality (VR) and robotic technologies. In limb rehabilitation, limb posture is required to (1) provide a limb realistic representation in VR games and (2) assess the patient improvement. When exoskeleton devices are used in the therapy, the measurements of their joint angles cannot be directly used to represent the posture of the patient limb, since the human and exoskeleton kinematic models differ. In response to this shortcoming, we propose a method to estimate the posture of the human limb attached to the exoskeleton. We use the exoskeleton joint angles measurements and the constraints of the exoskeleton on the limb to estimate the human limb joints angles. This paper presents (a) the mathematical formulation and solution to the problem, (b) the implementation of the proposed solution on a commercial exoskeleton system for the upper limb rehabilitation, (c) its integration into a rehabilitation VR game platform, and (d) the quantitative assessment of the method during elbow and wrist analytic training. Results show that this method properly estimates the limb posture to (i) animate avatars that represent the patient in VR games and (ii) obtain kinematic data for the patient assessment during elbow and wrist analytic rehabilitation.
[6]-Shogaol Inhibitsα-MSH-Induced Melanogenesis through the Acceleration of ERK and PI3K/Akt-Mediated MITF Degradation
Authors: Huang Huey-Chun , Chang Shu-Jen , Wu Chia-Yin , Ke Hui-Ju , Chang Tsong-Min
Published: July 2014

[6]-Shogaol is the main biologically active component of ginger. Previous reports showed that[6]-shogaol has several pharmacological characteristics, such as antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties. However, the effects of[6]-shogaol on melanogenesis remain to be elucidated. The study aimed to evaluate the potential skin whitening mechanisms of[6]-shogaol. The effects of[6]-shogaol on cell viability, melanin content, tyrosinase activity, and the expression of the tyrosinase and microphthalmia-associated transcription factor (MITF) were measured. The results revealed that[6]-shogaol effectively suppresses tyrosinase activity and the amount of melanin and that those effects are more pronounced than those of arbutin. It was also found that[6]-shogaol decreased the protein expression levels of tyrosinase-related protein 1 (TRP-1) and microphthalmia-associated transcriptional factor (MITF). In addition, the MITF mRNA levels were also effectively decreased in the presence of 20 μM[6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1-inhibitor (U0126) or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor) (LY294002). Further immunofluorescence staining assay implied the involvement of the proteasome in the downregulation of MITF by[6]-shogaol. Our confocal assay results also confirmed that[6]-shogaol inhibitedα-melanocyte stimulating hormone- (α-MSH-) induced melanogenesis through the acceleration of extracellular responsive kinase (ERK) and phosphatidylinositol-3-kinase- (PI3K/Akt-) mediated MITF degradation.
Preparation of Ginsenoside Rg3 and Protection against H2O2-Induced Oxidative Stress in Human Neuroblastoma SK-N-SH Cells
Authors: Li Gang , Zhang Xiao-xiao , Lin Lin , Liu Xiao-ning , Ma Cheng-jun , Li Ji , Wang Chi-bo
Published: July 2014

The aim of this study is to evaluate the protection of ginsenoside Rg3 against oxidative stress in human neuroblastoma SK-N-SH cells. 20(R)-ginsenoside Rg3 (20(R)-Rg3) and 20(S)-ginsenoside Rg3 (20(S)-Rg3) were prepared by the method of chemical degradation and column chromatography, and the structure of the two compounds was characterized by1H-NMR and13C-NMR spectroscopy. MTT assay and LDH leakage assay were used to determine the cell viability and the oxidative stress cellular model was established by means of H2O2(600 μM for 4 h). We also investigated the changes of intracellular MDA content, SOD activity, and ROS formation after the treatment of ginsenoside Rg3 for 20 h. The results indicated that both 20 (R)-Rg3 and 20 (S)-Rg3 had obvious protection against H2O2-induced oxidative stress in SK-N-SH cells. Moreover, 20(R)-Rg3 exhibited better antioxidant activity than 20(S)-Rg3in vitro. These findings are expected to provide some implication for further research and application of ginsenoside Rg3 in neuroprotection.
Acupuncture and Depth: Future Direction for Acupuncture Research
Authors: Goh You Li , Ho Chin Ee , Zhao Baixiao
Published: July 2014

The research on acupuncture has increased steadily over the years and regular review and revision of the direction of future acupuncture research are necessary. This paper aims to review and explore the significance of acupuncture depth in modern acupuncture research. Searches conducted in Science Direct and China National Knowledge Infrastructure (CNKI) databases reflected a lack of focus on depth of acupuncture. We propose that the research trends of acupuncture should progress to the depth of insertion. It is suggested that future acupuncture research, especially randomized controlled trials (RCTs), should take into consideration the depth of insertion. Comparison between databases using different language of medium suggests the need for international collaboration of researchers from the same field. It is also crucial to inherit and innovate traditional medicine (TM) through modern technology. The use of bibliometric method is also suitable for development of TM research trends. Acupuncture and depth should be considered as one of the future directions of acupuncture research.
Neurobiological Mechanisms of Pelvic Pain
Authors: Origoni Massimo , Leone Roberti Maggiore Umberto , Salvatore Stefano , Candiani Massimo
Published: July 2014

Pelvic pain is a common condition which significantly deteriorates health-related quality of life. The most commonly identified causes of pain in the pelvic region are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal. However, in up to 33% of patients the source of this symptom is not identified, frustrating both patients and health-care professionals. Pelvic pain may involve both the somatic and visceral systems, making the differential diagnosing challenging. This paper aimed to review the mechanisms involved in pelvic pain perception by analyzing the neural plasticity and molecules which are involved in these complex circuits.
Changes in Lipid Metabolism and Extension of Venous Thromboembolism
Authors: Belaj Klara , Hackl Gerald , Rief Peter , Eller Philipp , Brodmann Marianne , Gary Thomas
Published: July 2014

Background/Aims: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common diseases with a vast number of acquired and congenital risk factors. Disorders of the lipid metabolism are not established risk factors for venous thromboembolism (VTE) so far. However, in recent literature, associations between VTE and the metabolic syndrome, especially with elevated lipid parameters, have been described. The aim of our study was to investigate the association between the extension of VTE and changes in the lipid profile. Methods: We included 178 VTE patients in our study; 59 patients had isolated PE, 39 patients had isolated DVT of the leg and 80 patients had both (DVT and PE). Concerning PE, we distinguished between massive and submassive PE. We evaluated plasma lipids and lipoproteins in PE and DVT patients as well as in massive and submassive PE patients. Results: PE patients had higher levels of plasma triglycerides [median (interquartile range): 162 (109-254) vs. 136.5 (96.5-162) mg/dl, p = 0.047] and lower levels of high-density lipoprotein cholesterol (HDL-C; 52.1 ± 17.2 vs. 63.9 ± 22.7 mg/dl, p = 0.004) than DVT patients. Furthermore, PE patients were significantly older than DVT patients (59.6 ± 16.9 vs. 52.2 ± 15.5 years, p = 0.02). We were not able to find differences in lipid parameters in patients with massive PE compared to those with submassive PE. However, patients with massive PE were more obese than patients with submassive PE (body mass index 29.1 ± 4.6 vs. 26.9 ± 4.9, p = 0.012). Conclusions: Lipid parameters and lipoproteins differ between DVT and PE patients. PE patients had higher triglyceride and lower HDL-C levels compared with DVT patients.
FOLFIRINOX Bevacizumab Is a Promising Therapy for Chemorefractory Metastatic Colorectal Cancer
Authors: Chaix Marie , Vincent Julie , Lorgis Véronique , Ghiringhelli François
Published: July 2014

Purpose: Fluoropyrimidines, oxaliplatin, irinotecan and targeted therapies represent the standard treatment of metastatic colorectal cancer. After failure of all these treatments, few options are available. In such chemorefractory patients the effect of triplet chemotherapy with bevacizumab (FOLFIRINOX bevacizumab) has never been investigated. Patients and Methods: 49 consecutive patients bearing unresectable metastatic colorectal cancer and who experienced failure to oxaliplatin- and irinotecan-based chemotherapy were treated with oxaliplatin (85 mg/m2), irinotecan (180 mg/m2), leucovorin (400 mg/m2), and fluorouracil (400 mg/m2 bolus then 2,400 mg/m2) repeated every 2 weeks. Results: Median age was 63 (range 36-82) years. After a median follow-up of 12 months, the median progression-free survival was 5.8 months (95% CI 3.4-6.8) and the median overall survival was 11.9 months (95% CI 8-18). The response rate after the cycle was evaluable for 36 patients, whereby we observed 18% (95% CI 8-35) partial or complete response, 45% (95% CI 28-68) stable disease of more than 2 months, and 37% (95% CI 21-58) progression. Conclusion: This study suggests that bevacizumab + FOLFIRINOX may be active in mCRC patients after failure of classical lines of chemotherapy.
The Ketogenic Diet Modifies Social and Metabolic Alterations Identified in the Prenatal Valproic Acid Model of Autism Spectrum Disorder
Authors: Ahn Younghee , Narous Mariam , Tobias Rose , Rho Jong M. , Mychasiuk Richelle
Published: July 2014

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Although the etiology of ASD remains elusive, converging lines of research indicate that mitochondrial dysfunction may play a substantive role in disease pathophysiology. Without an established causal link, the generation of therapeutic targets for ASD has been relatively unsuccessful and has focused solely on individual symptoms. The ketogenic diet (KD) is a high-fat low-carbohydrate diet that has previously been used for the treatment of intractable epilepsy and is known to enhance mitochondrial function. The purpose of this study was to determine if the KD could reverse the social deficits and mitochondrial dysfunction identified in the prenatal valproic acid (VPA) rodent model of ASD. Sprague-Dawley dams were administered VPA or saline on gestational day 12.5. The pups were treated with the KD or their standard diet (SD) for 10 days beginning on postnatal day 21 (PD21). On PD35 juvenile play behavior was tested with the play-fighting paradigm and rats were then sacrificed for mitochondrial bioenergetic analysis. The offspring exposed to VPA prenatally demonstrated a significant decrease in the number of play initiations/attacks and this was reversed with the KD. Prenatal VPA exposure also disrupted the pattern of play responses; VPA/SD animals used complete rotations more often than saline control animals. Treatment with the KD did not affect the number of complete rotations. In addition, while prenatal exposure to VPA altered mitochondrial respiration, the KD was able to restore aspects of bioenergetic dysfunction. As the KD was able to modify complex social behaviors and mitochondrial respiration, it may be a useful treatment option for ASD. Future studies will need to examine the effectiveness of the KD to reverse the two additional core deficits of ASD and to explore various treatment regimens to determine optimal treatment duration and formulation.
Incidence of Cold-Induced Peripheral Neuropathy and Dose Modification of Adjuvant Oxaliplatin-Based Chemotherapy for Patients with Colorectal Cancer
Authors: Altaf Rahim , Lund Brixen Annette , Kristensen Bent , Nielsen Svend Erik
Published: July 2014

Background: The CAPOX regimen is used for adjuvant treatment of colorectal cancer. A well-known side effect of oxaliplatin, which often leads to dose modification (DM), is acute neuropathy (AN). AN is provoked by cold, and it could therefore be expected that the degree of AN and thereby DM is more pronounced in the winter period compared to the summer period. Method: Patients with colorectal cancer who received adjuvant CAPOX from January 2005 to August 2011 were reviewed. Out of 108 patients who received adjuvant CAPOX, the oxaliplatin dose was reduced in 92 (85%) patients due to AN. Seventeen out of 31 (55%) patients already had a DM of oxaliplatin in the second cycle during the winter period (December to February; mean temperature 0.1-1.8°C), while in the summer period (June to August; mean temperature 15.1-16.3°C), only 4 (13%) patients needed DM (OR = 2.5, p = 0.022). Conclusion: In this study, we found that the risk of DM and discontinuation of oxaliplatin is highest in the winter period compared to the other seasons. This study draws attention to the importance of training in the proper handling of the acute neurotoxicity of oxaliplatin.
A Serine Protease Homolog Negatively Regulates TEP1 Consumption in Systemic Infections of the Malaria Vector Anopheles gambiae
Authors: Yassine Hassan , Kamareddine Layla , Chamat Soulaima , Christophides George K. , Osta Mike A.
Published: July 2014

Clip domain serine protease homologs are widely distributed in insect genomes and play important roles in regulating insect immune responses, yet their exact functions remain poorly understood. Here, we show that CLIPA2, a clip domain serine protease homolog of Anopheles gambiae, regulates the consumption of the mosquito complement-like protein TEP1 during systemic bacterial infections. We provide evidence that CLIPA2 localizes to microbial surfaces in a TEP1-dependent manner whereby it negatively regulates the activity of a putative TEP1 convertase, which converts the full-length TEP1-F form into active TEP1cut. CLIPA2 silencing triggers an exacerbated TEP1-mediated response that significantly enhances mosquito resistance to infections with a broad class of microorganisms including Plasmodium berghei, Escherichia coli and the entomopathogenic fungus Beauveria bassiana. We also provide further evidence for the existence of a functional link between TEP1 and activation of hemolymph prophenoloxidase during systemic infections. Interestingly, the enhanced TEP1-mediated immune response in CLIPA2 knockdown mosquitoes correlated with a significant reduction in fecundity, corroborating the existence of a trade-off between immunity and reproduction. In sum, CLIPA2 is an integral regulatory component of the mosquito complement-like pathway which functions to prevent an overwhelming response by the host in response to systemic infections.
Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases
Authors: Neumann Ariane , Völlger Lena , Berends Evelien T.M. , Molhoek E. Margo , Stapels Daphne A.C. , Midon Marika , Friães Ana , Pingoud Alfred , Rooijakkers Suzan H.M. , Gallo Richard L. , Mörgelin Matthias , Nizet Victor , Naim Hassan Y. , von Köckritz-Blickwede Maren
Published: July 2014

Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 and human neutrophil peptide-1 showed similar protection of neutrophil-derived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: beside its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-derived DNA or NETs against bacterial nuclease degradation.
A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer
Authors: Kroeber Vinzenz , Nagel Sylke , Schuette Wolfgang , Blankenburg Thomas
Published: July 2014

Introduction: Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Methods: Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m2 followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m2. Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. Results: The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. Conclusions: We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered.
Severe Colitis Associated with both Epstein-Barr Virus and Cytomegalovirus Reactivation in a Patient with Severe Aplastic Anemia
Authors: Matsumoto Hiroshi , Kimura Yoshiki , Murao Takahisa , Osawa Motoyasu , Akiyama Takashi , Mannoji Kiyohito , Koresawa Risa , Tokunaga Hirotoshi , Wada Hideho , Sugihara Takashi , Haruma Ken
Published: July 2014

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD.
Public and Elite Perceptions of Supranational Courts: The European Perspective
Authors: Grødeland Åse B.
Published: July 2014

This article investigates the perceptions of legal insiders (i.e., those working professionally with law) and legal outsiders (i.e., those affected by law) of European supranational courts in general, and the European Court of Human Rights (ECtHR) in particular. Drawing on largescale qualitative and quantitative data collected in Norway, UK, Poland, Bulgaria and Ukraine, the article shows that support for such courts is widespread across Europe—though less so in the UK than elsewhere. Support is predominantly ‘informed’ by practical considerations of usefulness rather than by ideology. Our data suggest that national legal cultures are highly responsive to ECtHR case law as a legal transfer. This, in turn, has implications for the debate on the legitimacy of the ECtHR and, thus, also for its future.
Observations on the biology of Afrotropical Hesperiidae (Lepidoptera). Part 6. Hesperiinae incertae sedis: palm feeders
Authors: COCK MATTHEW J.W. , CONGDON T. COLIN E. , COLLINS STEVE C.
Published: July 2014

Partial life histories for 12 Hesperiinae incertae sedis that feed on palms (Arecaceae) are described and illustrated. The genera dealt with are: Perrotia (part), Ploetzia, Zophopetes, Gretna (part), Pteroteinon, Leona, and Caenides (part) (all from Evans’ Ploetzia genera group). Although Gamia spp. have been reported to feed on palms, these records are considered to be in error, as caterpillars of this genus feed on Dracaena spp. (Asparagaceae). The life histories of the species documented are fairly uniform, in that caterpillars of most species have rounded brown heads, wider basally, with or without limited black markings, smooth bodies and make simple shelters by rolling leaves. Variation in caterpillar markings and male genitalia of Zophopetes dysmephila (Trimen) and caterpillar and adult markings of Gretna carmen Evans merit further study. In G. carmen, G. waga (Plötz) and G. balenge (Holland), the caterpillars’ head and body are covered with hair-like setae, and develop an extensive covering of white waxy powder, which in G. balenge also covers the long setae. Furthermore, the pupa of G. balenge is unusual in having a pair of large, elaborate processes frontally on the head; when disturbed, the pupa vibrates violently and rattles noisily against the sides of the shelter. Ploetzia amygdalis (Mabille) and Pteroteinon laufella (Hewitson) have gregarious caterpillars, whereas the remaining species are solitary. After eclosion, the first instar caterpillars of Gretna spp. moult to the second instar without feeding. The implications of a palm-feeding life-style are discussed, and economic damage and plant quarantine risks to coconut, oil palm and ornamental palms pointed out. The known life histories suggest that all Afrotropical palm-feeding Hesperiidae will belong in the same tribe when the incertae sedis section is further elucidated, although the affinities of Gretna deserve further consideration.
“I see it now”: Using photo elicitation to understand chronic illness self-management
Authors: Fritz Heather , Lysack Cathy
Published: July 2014

Background.

How people integrate self-management into daily life remains underexamined, and such processes are difficult to elicit through traditional approaches used to understand human occupation.

Purpose.

This paper will provide a brief overview of one visual research method, photo elicitation, that holds promise for studying self-management of health behaviours and will present findings from an analysis of how the use of photo elicitation interviews contributed additional insights into self-management beyond those generated from the data collected through the other methods used in the study.

Method.

A qualitative, multiple-methods, multiple-case study was conducted with a purposive sample of 10 low-income women ages 40 to 64 with type 2 diabetes.

Findings.

The photo elicitation interviews contributed insights beyond those generated from other study methods about how individuals viewed their self-management behaviours and how occupations changed across time.

Implications.

Photo elicitation is a valuable research method for better understanding clients’ chronic illness self-management practices.
Simultaneous subcutaneous implantation of two osmotic minipumps connected to a jugular vein catheter in the rat
Authors: Wedel Johannes , Weij Michel , Oosten Annemieke Smit-van , Hillebrands Jan-Luuk
Published: July 2014

Subcutaneous osmotic pump implantation connected to a venous catheter is a well-established method for delivering compounds intravenously for an intermediate duration (approximately two weeks). When prolonged release is desired (approximately four weeks) reduced flow rate is needed with a similar pump volume. With a fixed intra-pump compound concentration, reduced flow rate results in unwanted reduced bioavailability of the compound. Prolonged intravenous delivery would therefore need a pump replacement, resulting in increased discomfort and confounding effects on experimental outcome. To overcome this, we describe a method to double the compound infusion rate for four weeks by implanting two low-flow rate osmotic pumps (2.5 µL/h for 28 days) connected to a jugular vein catheter in a single rat. Rats implanted with a single high-flow rate pump (5 µL/h for 14 days) served as controls. Double pump-implanted rats displayed similar post-operative weight gain and physical activity indicating similar levels of discomfort when compared with single pump-implanted rats. Double pump-implanted rats had an increased risk of pump-related complications (four delivery failures [double pump] versus one delivery failure [single pump]). Our data show that double pump implantation is a feasible alternative to changing pumps or the use of extracorporeal pump systems connected via a long wire to partly restrained animals.
The voice of the visitor: Popular reactions to the exhibition Vernichtungskrieg. Verbrechen der Wehrmacht 1941–1944
Authors: Nugent Christine R.
Published: July 2014

This paper examines popular reactions to the so-called Wehrmachtsausstellung through the lens of entries in the exhibition’s visitors’ books. The majority of such entries are informed by visitors’ generational identity vis-à-vis National Socialism. Harlad Welzer’s theory of memory, derived from his studies of multi-generational family discourse about the Nazi past, provides a framework for analysing the entries. Similarities and differences emerge between Welzer’s observations and the entries in the visitors’ books. While the books represent just one among many possible sources that shed light on popular reactions to the exhibition, they nevertheless provide a fruitful source of enquiry for an understanding of the dynamic between public history and individual/family memory in the construction of historical consciousness about the legacy of National Socialism.
Nutrition and mental performance in children – The NUTRIMENTHE project
Authors: Horton Claire
Published: July 2014

The Nutrition And Mental Performance In Children project of the European Union (NUTRIMENTHE) has added to the evidence that maternal diet influences mental performance in childhood. The biological mechanisms have been shown to be complex and to involve genetic variation, as indicated by the work linking genetic variation in the fatty acid desaturase gene cluster to the processing of fatty acids. The role played by a child’s diet also needs to be considered and this question is being addressed through the inclusion of post-natal intervention studies in the NUTRIMENTHE project's research plan. This paper summarises progress.
Long-term Results of Autologous Chondrocyte Implantation in the Knee for Chronic Chondral and Osteochondral Defects
Authors: Biant Leela C. , Bentley George , Vijayan Sridhar , Skinner John A. , Carrington Richard W.J.
Published: July 2014

Background:

Autologous chondrocyte implantation (ACI) has been shown to be effective in the midterm for the treatment of symptomatic articular cartilage lesions of the knee, but few long-term series have been published. The multioperated chronic articular cartilage defect remains a difficult condition to treat.

Purpose:

To examine the long-term clinical results of ACI for large chronic articular cartilage defects, many treated as salvage.

Study Design:

Case series; Level of evidence, 4.

Methods:

This is a prospective case series of 104 patients with a mean age of 30.2 years and a symptomatic lesion of the articular cartilage in the knee, who underwent ACI between 1998 and 2001. The mean duration of symptoms before surgery was 7.8 years. The mean number of previous surgical procedures on the cartilage defect, excluding arthroscopic debridement, was 1.3. The defects were large, with a mean size of 477.1 mm2 (range, 120-2500 mm2). The modified Cincinnati, Stanmore/Bentley, and visual analog scale for pain scoring systems were used to assess pain and functional outcomes at a minimum 10 years (mean, 10.4 years; range, 10-12 years).

Results:

Twenty-seven patients (26%) experienced graft failure at a mean of 5.7 years after ACI. Of the 73 patients who did not fail, 46 patients (63% of patients with a surviving graft) had an excellent result, 18 (25%) were good, 6 (8%) were fair, and 3 (4%) had a poor result. Of a total of 100 patients successfully followed up, 98 were satisfied with the ACI technique for their chronic knee pain and would undergo the procedure again.

Conclusion:

Autologous chondrocyte implantation can provide a long-term solution in more than 70% of young patients of a difficult-to-treat group with large chronic articular cartilage lesions, even in the salvage situation.