bluuebunny/crossref_metadata_2025 huggingface dataset:
Excretion of Host DNA in Feces Is Associated with Risk ofClostridium difficileInfection
Authors: Vincent Caroline , Mehrotra Sudeep , Loo Vivian G. , Dewar Ken , Manges Amee R.
Published: May 2015

Clostridium difficileinfection (CDI) is intricately linked to the health of the gastrointestinal tract and its indigenous microbiota. In this study, we assessed whether fecal excretion of host DNA is associated with CDI development. Assuming that shedding of epithelial cell increases in the inflamed intestine, we used human DNA excretion as a marker of intestinal insult. Whole-genome shotgun sequencing was employed to quantify host DNA excretion and evaluate bacterial content in fecal samples collected from patients with incipient CDI, hospitalized controls, and healthy subjects. Human DNA excretion was significantly increased in patients admitted to the hospital for a gastrointestinal ailment, as well as prior to an episode of CDI. In multivariable analyses, human read abundance was independently associated with CDI development. Host DNA proportions were negatively correlated with intestinal microbiota diversity.EnterococcusandEscherichiawere enriched in patients excreting high quantities of human DNA, whileRuminococcusandOdoribacterwere depleted. These findings suggest that intestinal inflammation can occur prior to CDI development and may influence patient susceptibility to CDI. The quantification of human DNA in feces could serve as a simple and noninvasive approach to assess bowel inflammation and identify patients at risk of CDI.
On the Approximate Controllability of Fractional Evolution Equations with Generalized Riemann-Liouville Fractional Derivative
Authors: Mahmudov N. I. , McKibben M. A.
Published: May 2015

We discuss the approximate controllability of fractional evolution equations involving generalized Riemann-Liouville fractional derivative. The results are obtained with the help of the theory of fractional calculus, semigroup theory, and the Schauder fixed point theorem under the assumption that the corresponding linear system is approximately controllable. Finally, an example is provided to illustrate the abstract theory.
Interleukin-23Rrs7517847 T/G Polymorphism Contributes to the Risk of Crohn’s Disease in Caucasians: A Meta-Analysis
Authors: Zhang Li , Lu Yunjie , Ge Yuzheng , Shi Yun , Wu Xing , Xu Qinghua , Li Xiaoping , Lu Ling , Zhang Feng , Yao Guozhong
Published: May 2015

The association betweenInterleukin-23Rgene polymorphism and Crohn’s disease (CD) in Caucasians is still controversial. Thus, a meta-analysis was performed to evaluate the correlation between this gene variant and CD risk. We retrieved the available data from EMBASE and PUBMED until May 1, 2014, and evaluated the effect of rs7517847 in Caucasians. The significant associations were confirmed between rs7517847 and CD risk in dominant models (TT/TG versus GG: OR = 1.652, 95% CI 1.277, 2.137), allelic model (T allele versus G allele: OR = 1.327, 95% CI 1.198, 1.469), homozygote comparison (TT versus GG: OR = 1.890, 95% CI 1.465, 2.437), heterozygote comparison (TG versus GG: OR = 1.509, 95% CI 1.161, 1.960), and recessive model (TT versus TG/GG: OR = 1.409, 95% CI 1.279, 1.552). In conclusion, this meta-analysis demonstrates that rs7517847 is associated with the risk of CD in Caucasians. These findings show that IL-23R genes confer susceptibility to CD in the Caucasians.
RRM2B‐Mediated Regulation of Mitochondrial Activity and Inflammation under Oxidative Stress
Authors: Cho Er-Chieh , Kuo Mei-Ling , Cheng Jia-hui , Cheng Yu-Chi , Hsieh Yi-Chen , Liu Yun-Ru , Hsieh Rong-Hong , Yen Yun
Published: May 2015

RRM2B is a critical ribonucleotide reductase (RR) subunit that exists as p53‐inducible and p53‐dependent molecule. The p53‐independent regulation of RRM2B has been recently studied, and FOXO3 was identified as a novel regulator of RRM2B. However, the p53‐independent regulation of RRM2B, particularly under oxidative stress, remains largely unknown. In this study, we investigated the role of RRM2B underoxidative stress‐induced DNA damage and further examined the regulation of mitochondrial and inflammatory genes by RRM2B. Our study is the first to report the critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a p53‐independent manner. Furthermore, our study provides novel insights into the role of the RR in inflammatory diseases.
Future Changes in Human-Biometeorological Index Classes in Three Regions of Luxembourg, Western-Central Europe
Authors: Lokys Hanna Leona , Junk Jürgen , Krein Andreas
Published: May 2015

Projected climate change will cause increasing air temperatures affecting human thermal comfort. In the highly populated areas of Western-Central Europe a large population will be exposed to these changes. In particular Luxembourg—with its dense population and the large cross-border commuter flows—is vulnerable to changing thermal stress. Based on climate change projections we assessed the impact of climate change on human thermal comfort over the next century using two common human-biometeorological indices, the Physiological Equivalent Temperature and the Universal Thermal Climate Index. To account for uncertainties, we used a multimodel ensemble of 12 transient simulations (1971–2098) with a spatial resolution of 25 km. In addition, the regional differences were analysed by a single regional climate model run with a spatial resolution of 1.3 km. For the future, trends in air temperature, vapour pressure, and both human-biometeorological indices could be determined. Cold stress levels will decrease significantly in the near future up to 2050, while the increase in heat stress turns statistically significant in the far future up to 2100. This results in a temporarily reduced overall thermal stress level but further increasing air temperatures will shift the thermal comfort towards heat stress.
Real-Time Inverse Optimal Neural Control for Image Based Visual Servoing with Nonholonomic Mobile Robots
Authors: López-Franco Carlos , López-Franco Michel , Alanis Alma Y. , Gómez-Avila Javier , Arana-Daniel Nancy
Published: May 2015

We present an inverse optimal neural controller for a nonholonomic mobile robot with parameter uncertainties and unknown external disturbances. The neural controller is based on a discrete-time recurrent high order neural network (RHONN) trained with an extended Kalman filter. The reference velocities for the neural controller are obtained with a visual sensor. The effectiveness of the proposed approach is tested by simulations and real-time experiments.
Double-Layered Lateral Meniscus Accompanied by Meniscocapsular Separation
Authors: Fukuda Aki , Nishimura Akinobu , Nakazora Shigeto , Kato Ko , Sudo Akihiro
Published: May 2015

We report an extremely rare case of double-layered lateral meniscus accompanied by meniscocapsular separation. The upper accessory meniscus was connected with the posterior horn and middle segment of the lower normal meniscus and was more mobile than the lower normal meniscus. A meniscocapsular separation was evident at the overlapping middle segment. Clinical symptoms were significantly improved by the resection of the upper accessory meniscus and the repair of the meniscocapsular separation. Careful arthroscopic analysis of other associated pathologies together with this rare abnormality was needed to achieve clinical improvement.
Uniphasic Blanching of the Fingers, Abnormal Capillaroscopy in Nonsymptomatic Digits, and Autoantibodies: Expanding Options to Increase the Level of Suspicion of Connective Tissue Diseases beyond the Classification of Raynaud’s Phenomenon
Authors: Ingegnoli Francesca , Gualtierotti Roberta , Orenti Annalisa , Schioppo Tommaso , Marfia Giovanni , Campanella Rolando , Mastaglio Claudio , Meroni Pier Luigi , Boracchi Patrizia
Published: May 2015

In patients with Raynaud’s phenomenon (RP), the role of medical history, capillaroscopy, and autoantibodies in order to provide an early diagnosis of connective tissue disease (CTD) were examined. 115 consecutive adults with uni-, bi-, or triphasic colour changes of the fingers were studied. RP was bilateral in 92.7% of patients. The middle finger was significantly more affected. A lack of association between fingers affected by RP and fingers with capillary abnormalities was observedOR=0.75(0.34–1.66). RP with the cyanotic phase had a higher risk at capillaroscopy to have hemorrhagesOR=4.46(1.50–13.30) and giant capillariesOR=24.85(1.48–417.44). The thumb and triphasic involvement have an OR of 1.477 and 1.845, respectively. RP secondary to systemic sclerosis (SSc) had greater value of VAS pain (p=0.011). The presence of anti-centromere antibodies was significantly associated with a higher risk of SSc (p<0.001). 44.3% of subjects had uniphasic blanching of the fingers, and among these, 27% was diagnosed as having an overt or suspected CTD. Markers of a potential development of CTDs include severe RP symptoms, positive autoantibodies, and capillary abnormalities. These data support the proposal to not discharge patients with uniphasic blanching of the fingers to avoid missing the opportunity of an early diagnosis.
Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria
Authors: Ljubic Spomenka , Jazbec Anamarija , Tomic Martina , Piljac Ante , Jurisic Erzen Dubravka , Novak Branko , Kastelan Snjezana , Lovrencic Marijana Vucic , Brkljacic Neva
Published: May 2015

Aims.To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy.Methods.ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients.Results.Significant differences among ApN levels according to AER were found in both types of diabetes (F=8.45,df=2,P<0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F=12.7,df=1,P<0.001). The best model for ApN (R2=0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R2=0.2882) it included ppPG, LDL, and UA.Conclusion.ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes.
WNT/β-Catenin Signaling Is Required for Integration of CD24+Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules
Authors: Zhang Zhao , Iglesias Diana M. , Corsini Rachel , Chu LeeLee , Goodyer Paul
Published: May 2015

During development, nephron progenitor cells (NPC) are induced to differentiate by WNT9b signals from the ureteric bud. Although nephrogenesis ends in the perinatal period, acute kidney injury (AKI) elicits repopulation of damaged nephrons. Interestingly, embryonic NPC infused into adult mice with AKI are incorporated into regenerating tubules. Since WNT/β-catenin signaling is crucial for primary nephrogenesis, we reasoned that it might also be needed for the endogenous repair mechanism and for integration of exogenous NPC. When we examined glycerol-induced AKI in adult mice bearing aβ-catenin/TCF reporter transgene, endogenous tubular cells reexpressed the NPC marker, CD24, and showed widespreadβ-catenin/TCF signaling. We isolated CD24+cells from E15 kidneys of mice with the canonical WNT signaling reporter. 40% of cells responded to WNT3ain vitroand when infused into glycerol-injured adult, the cells exhibitedβ-catenin/TCF reporter activity when integrated into damaged tubules. When embryonic CD24+cells were treated with aβ-catenin/TCF pathway inhibitor (IWR-1) prior to infusion into glycerol-injured mice, tubular integration of cells was sharply reduced. Thus, the endogenous canonicalβ-catenin/TCF pathway is reactivated during recovery from AKI and is required for integration of exogenous embryonic renal progenitor cells into damaged tubules. These events appear to recapitulate the WNT-dependent inductive process which drives primary nephrogenesis.
Prefrontal Hemodynamic Changes Associated with Subjective Sense of Occlusal Discomfort
Authors: Ono Yumie , Kobayashi Goh , Hayama Rika , Ikuta Ryuhei , Onozouka Minoru , Wake Hiroyuki , Shimada Atsushi , Shibuya Tomoaki , Tamaki Katsushi
Published: May 2015

We used functional near-infrared spectroscopy to measure prefrontal brain activity accompanying the physical sensation of oral discomfort that arose when healthy young-adult volunteers performed a grinding motion with mild occlusal elevation (96 μm). We simultaneously evaluated various forms of occlusal discomfort using the visual analogue scale (VAS) and hemodynamic responses to identify the specific prefrontal activity that occurs with increased occlusal discomfort. The Oxy-Hb responses of selected channels in the bilateral frontopolar and dorsolateral prefrontal cortices increased in participants who reported increased severity of occlusal discomfort, while they decreased in those who reported no change or decreased occlusal discomfort during grinding. Moreover, the cumulative values of Oxy-Hb response in some of these channels were statistically significant predictive factors for the VAS scores. A generalized linear model analysis of Oxy-Hb signals in a group of participants who reported increased discomfort further indicated significant cerebral activation in the right frontopolar and dorsolateral prefrontal cortices that overlapped with the results of correlation analyses. Our results suggest that the increased hemodynamic responses in the prefrontal area reflect the top-down control of attention and/or self-regulation against the uncomfortable somatosensory input, which could be a possible marker to detect the subjective sense of occlusal discomfort.
Frequency of Electrolyte Derangement after Transurethral Resection of Prostate: Need for Postoperative Electrolyte Monitoring
Authors: Aziz Wajahat , Ather M. Hammad
Published: May 2015

Objective. To determine the electrolyte derangement following transurethral resection of prostate (TURP).Methods. All patients undergoing TURP from June 2012 to April 2013 were included. Preoperative electrolytes were performed within a week of procedures. Monopolar TURP using 1.5% glycine was performed. Serum Na+and K+were assessed within 1 hour postoperatively and subsequently if clinically indicated.Results. The study included 280 patients. Sixty-six patients (23.6%) had electrolyte derangement after TURP. Patients with deranged electrolytes were older (mean age of 73.41 ± 4.08 yrs. versus 68.93 yrs. ± 10.34) and had a longer mean resection time (42.5 ± 20.04 min versus 28.34 ± 14.64 min). Mean weight of tissue resected (41.49 ± 34.46 g versus 15.33 ± 9.74 g) and volume of irrigant used (23.55 ± 15.20 L versus 12.81 ± 7.57 L) were also significantly higher in patients with deranged electrolytes (allp=0.00). On multivariate logistic regression analysis preoperative sodium level was found to be a significant predictor of postoperative electrolyte derangement (odds ratio 0.267, S.E. = 0.376, andpvalue = 0.00).Conclusion. Electrolyte derangement occurs in older patients, with larger amount of tissue and longer time of resection and higher volume of irrigant, and in those with lower serum preoperative sodium levels.
Determination of Oleanolic and Ursolic Acids inHedyotis diffusaUsing Hyphenated Ultrasound-Assisted Supercritical Carbon Dioxide Extraction and Chromatography
Authors: Wei Ming-Chi , Yang Yu-Chiao , Hong Show-Jen
Published: May 2015

Oleanolic acid (OA) and ursolic acid (UA) were extracted fromHedyotis diffusausing a hyphenated procedure of ultrasound-assisted and supercritical carbon dioxide (HSC–CO2) extraction at different temperatures, pressures, cosolvent percentages, and SC–CO2flow rates. The results indicated that these parameters significantly affected the extraction yield. The maximal yields of OA (0.917 mg/g of dry plant) and UA (3.540 mg/g of dry plant) were obtained at a dynamic extraction time of 110 min, a static extraction time of 15 min, 28.2 MPa, and 56°C with a 12.5% (v/v) cosolvent (ethanol/water = 82/18, v/v) and SC–CO2flowing at 2.3 mL/min (STP). The extracted yields were then analyzed by high performance liquid chromatography (HPLC) to quantify the OA and UA. The present findings revealed thatH. diffusais a potential source of OA and UA. In addition, using the hyphenated procedure for extraction is a promising and alternative process for recovering OA and UA fromH. diffusaat high concentrations.
Effects of Total Ginsenosides on the Feeding Behavior and Two Enzymes Activities ofMythimna separata(Walker) Larvae
Authors: Zhang Ai-Hua , Tan Shi-Qiang , Zhao Yan , Lei Feng-Jie , Zhang Lian-Xue
Published: May 2015

Ginsenosides, the main effective components ofPanax ginsengC.A. Meyer andPanax quinquefoliusL., are important allelochemicals ofginseng. Although many studies have targeted the pharmacological, chemical, and clinical properties of ginsenosides, little is known about their ecological role inginsengpopulation adaptation and evolution. Pests rarely feed onginseng, and it is not known why. This study investigated the effects of total ginsenosides on feeding behavior and activities of acetylcholinesterase (AChE) and glutathione s-transferase (GST) inMythimna separata(Walker) larvae. The results showed that the total ginsenosides had significant antifeeding activity againstM. separatalarvae, determined by nonselective and selective antifeeding bioassays. In addition, the total ginsenosides had inhibitory effects on the activities of GST and AChE. The antifeeding ratio was the highest at 8 h, then decreased, and was the lowest at 16 h. Both GST and AChE activities decreased from 0 h to 48 h in all total ginsenosides treatments but increased at 72 h. Total ginsenosides had antifeeding activity againstM. separatalarvae and inhibitory effects on the activities of GST and AChE.
Strategies of Intracellular Pathogens for Obtaining Iron from the Environment
Authors: Leon-Sicairos Nidia , Reyes-Cortes Ruth , Guadrón-Llanos Alma M. , Madueña-Molina Jesús , Leon-Sicairos Claudia , Canizalez-Román Adrian
Published: May 2015

Most microorganisms are destroyed by the host tissues through processes that usually involve phagocytosis and lysosomal disruption. However, some organisms, called intracellular pathogens, are capable of avoiding destruction by growing inside macrophages or other cells. During infection with intracellular pathogenic microorganisms, the element iron is required by both the host cell and the pathogen that inhabits the host cell. This minireview focuses on how intracellular pathogens use multiple strategies to obtain nutritional iron from the intracellular environment in order to use this element for replication. Additionally, the implications of these mechanisms for iron acquisition in the pathogen-host relationship are discussed.
How the Intricate Interaction among Toll-Like Receptors, Microbiota, and Intestinal Immunity Can Influence Gastrointestinal Pathology
Authors: Frosali Simona , Pagliari Danilo , Gambassi Giovanni , Landolfi Raffaele , Pandolfi Franco , Cianci Rossella
Published: May 2015

The gut is able to maintain tolerance to microbial and food antigens. The intestine minimizes the number of harmful bacteria by shaping the microbiota through a symbiotic relationship. In healthy human intestine, a constant homeostasis is maintained by the perfect regulation of microbial load and the immune response generated against it. Failure of this balance may result in various pathological conditions. Innate immune sensors, such as Toll-like receptors (TLRs), may be considered an interface among intestinal epithelial barrier, microbiota, and immune system. TLRs pathway, activated by pathogens, is involved in the pathogenesis of several infectious and inflammatory diseases. The alteration of the homeostasis between physiologic and pathogenic bacteria of intestinal flora causes a condition called dysbiosis. The breakdown of homeostasis by dysbiosis may increase susceptibility to inflammatory bowel diseases. It is evident that environment, genetics, and host immunity form a highly interactive regulatory triad that controls TLR function. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes, such as in IBD, colitis, and colorectal cancer. The study of interactions between different components of the immune systems and intestinal microbiota will open new horizons in the knowledge of gut inflammation.
Twenty Years of Schizophrenia Research in the Northern Finland Birth Cohort 1966: A Systematic Review
Authors: Jääskeläinen Erika , Haapea Marianne , Rautio Nina , Juola Pauliina , Penttilä Matti , Nordström Tanja , Rissanen Ina , Husa Anja , Keskinen Emmi , Marttila Riikka , Filatova Svetlana , Paaso Tiina-Mari , Koivukangas Jenni , Moilanen Kristiina , Isohanni Matti , Miettunen Jouko
Published: May 2015

Birth cohort designs are useful in studying adult disease trajectories and outcomes, such as schizophrenia. We review the schizophrenia research performed in the Northern Finland Birth Cohort 1966 (NFBC 1966), which includes 10,934 individuals living in Finland at 16 years of age who have been monitored since each mother’s mid-pregnancy. By the age of 44, 150 (1.4%) had developed schizophrenia. There are 77 original papers on schizophrenia published from the NFBC 1966. The early studies have found various risk factors for schizophrenia, especially related to pregnancy and perinatal phase. Psychiatric and somatic outcomes were heterogeneous, but relatively poor. Mortality in schizophrenia is high, especially due to suicides. Several early predictors of outcomes have also been found. Individuals with schizophrenia have alterations in brain morphometry and neurocognition, and our latest studies have found that the use of high lifetime doses of antipsychotics associated with these changes. The schizophrenia research in the NFBC 1966 has been especially active for 20 years, the prospective study design and long follow-up enabling several clinically and epidemiologically important findings. When compared to other birth cohorts, the research in the NFBC 1966 has offered also unique findings on course and outcome of schizophrenia.
Inguinal Herniation of the Urinary Bladder Presenting as Recurrent Urinary Retention
Authors: Frenkel Amit , Roy-Shapira Aviel , Shelef Ilan , Shaked Gadi , Brotfain Evgeni , Koyfman Leonid , Borer Abraham , Klein Moti
Published: May 2015

Herniation of the urinary bladder into the inguinal canal is an uncommon finding, observed in 0.5–4% of inguinal hernias (Curry (2000)). It is usually associated with other conditions that increase intra-abdominal pressure such as bladder neck obstruction due to prostatic hypertrophy. Consequently, in men, it is usually associated with some degree of urinary retention. We present a 42-year-old man in whom herniation of the urinary bladder was the cause of urinary retention, and not vice versa. The patient was on tumor necrosis factor alpha antagonist (TNFA) (Etanercept) for severe Ankylosing spondylitis. Initially, the urinary retention was thought to be a side effect of the medication, but after the drug was discontinued, urinary retention persisted. CT and MRI demonstrated huge herniation of the urinary bladder into the inguinal canal. Immediately after the hernia was repaired, bladder function was restored. TNF treatment was restarted, and no further urinary symptoms were observed in the next two years of follow-up. In this case, the primary illness and its treatment were distracting barriers to early diagnosis and treatment. In younger patients with a large hernia who develop unexpected urinary retention, herniation of the urinary bladder should be highly considered in the differential diagnosis.
Accidental Durotomy in Minimally Invasive Transforaminal Lumbar Interbody Fusion: Frequency, Risk Factors, and Management
Authors: Klingler Jan-Helge , Volz Florian , Krüger Marie T. , Kogias Evangelos , Rölz Roland , Scholz Christoph , Sircar Ronen , Hubbe Ulrich
Published: May 2015

Purpose. To assess the frequency, risk factors, and management of accidental durotomy in minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Methods. This single‐center study retrospectively investigates 372 patients who underwent MIS TLIF and were mobilized within 24 hours after surgery. The frequency of accidental durotomies, intraoperative closure technique, body mass index, and history of previous surgery was recorded. Results. We identified 32 accidental durotomies in 514 MIS TLIF levels (6.2%). Analysis showed a statistically significant relation of accidental durotomies to overweight patients (body mass index ≥25 kg/m2; P = 0.0493). Patient age older than 65 years tended to be a positive predictor for accidental durotomies (P = 0.0657). Mobilizing patients on the first postoperative day, we observed no durotomy‐associated complications. Conclusions. The frequency of accidental durotomies in MIS TLIF is low, with overweight being a risk factor for accidental durotomies. The minimally invasive approach seems to minimize durotomy‐associated complications (CSF leakage, pseudomeningocele) because of the limited dead space in the soft tissue. Patients with accidental durotomy can usually be mobilized within 24 hours after MIS TLIF without increased risk. The minimally invasive TLIF technique might thus be beneficial in the prevention of postoperative immobilization‐associated complications such as venous thromboembolism. This trial is registered with DRKS00006135.
Atlas of Cellular Dynamics during Zebrafish Adult Kidney Regeneration
Authors: McCampbell Kristen K. , Springer Kristin N. , Wingert Rebecca A.
Published: May 2015

The zebrafish is a useful animal model to study the signaling pathways that orchestrate kidney regeneration, as its renal nephrons are simple, yet they maintain the biological complexity inherent to that of higher vertebrate organisms including mammals. Recent studies have suggested that administration of the aminoglycoside antibiotic gentamicin in zebrafish mimics human acute kidney injury (AKI) through the induction of nephron damage, but the timing and details of critical phenotypic events associated with the regeneration process, particularly in existing nephrons, have not been characterized. Here, we mapped the temporal progression of cellular and molecular changes that occur during renal epithelial regeneration of the proximal tubule in the adult zebrafish using a platform of histological and expression analysis techniques. This work establishes the timing of renal cell death after gentamicin injury, identifies proliferative compartments within the kidney, and documents gene expression changes associated with the regenerative response of proliferating cells. These data provide an important descriptive atlas that documents the series of events that ensue after damage in the zebrafish kidney, thus availing a valuable resource for the scientific community that can facilitate the implementation of zebrafish research to delineate the mechanisms that control renal regeneration.
FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease
Authors: Kuo Ho-Chang , Hsu Yu-Wen , Wu Mei-Shin , Woon Peng Yeong , Wong Henry Sung-Ching , Tsai Li-Jen , Lin Ruo-Kai , Klahan Sukhontip , Hsieh Kai-Sheng , Chang Wei-Chiao
Published: May 2015

Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II‐a (FCGR2A) gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out‐patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF‐kB, Myc‐Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.
Chinese Herbal Medicine Combined with Conventional Therapy for Blood Pressure Variability in Hypertension Patients: A Systematic Review of Randomized Controlled Trials
Authors: Chen Zhuo , Wang Liqiong , Yang Guoyan , Xu Hao , Liu Jianping
Published: May 2015

Objective. The aim of this systematic review is to evaluate effect of Chinese medicine combined with conventional therapy on blood pressure variability (BPV) in hypertension patients.Methods. All randomized clinical trials (RCTs) comparing Chinese medicine with no intervention or placebo on the basis of conventional therapy were included. Data extraction, analyses, and quality assessment were performed according to the Cochrane standards.Results. We included 13 RCTs and assessed risk of bias for all the trials. Chinese medicine has a significant effect in lowering blood pressure (BP), reducing BPV in the form of standard deviation (SD) or coefficient of variability (CV), improving nighttime BP decreased rate, and reversing abnormal rhythm of BP.Conclusions. Chinese medicine was safe and showed beneficial effects on BPV in hypertension patients. However, more rigorous trials with high quality are warranted to give high level of evidence before recommending Chinese medicine as an alternative or complementary medicine to improve BPV in hypertension patients.
Magnetic Bead-Based Serum Peptidome Profiling in Patients with Gestational Diabetes Mellitus
Authors: Ai Tingting , Chen Feng , Zhou Shaonan , Zhang Jieni , Zheng Hui , Zhou Yanheng , Hu Wei , Liu Xiaofei , Li Li , Lin Jiuxiang
Published: May 2015

Gestational diabetes mellitus (GDM) is a frequent medical condition during pregnancy. Early diagnosis and treatment of GDM are crucial for both the mother and the baby. In the present study, we aimed to identify specific biomarkers to assist in the early detection of GDM and give some clues to the possible causes of GDM by comparing serum peptide profile differences between GDM patients and healthy controls. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used in combination with weak cation exchange magnetic bead (WCX-MB). Levels of four peptides (4418.9, 2219.7, 2211.5, and 1533.4 Da) were significantly different. Interestingly, three of them (4418.9, 2211.5, and 1533.4 Da) were identified when GDM patients with two degrees of glucose intolerance were compared. Additionally, peptides 2211.5 and 1533.4 Da showed a decreasing trend as glucose intolerance increased, while peptide 4418.9 Da exhibited the reverse tendency. In conclusion, our study provides novel insights into the altered serum peptide profile of GDM patients. The specific candidate biomarkers may contribute to the development of GDM.
Development of an IP-Free Biotechnology Platform for Constitutive Production of HPV16 L1 Capsid Protein Using thePichia pastoris PGK1Promoter
Authors: Mariz F. C. , Coimbra E. C. , Jesus A. L. S. , Nascimento L. M. , Torres F. A. G. , Freitas A. C.
Published: May 2015

The human papillomavirus (HPV) L1 major capsid protein, which forms the basis of the currently available vaccines against cervical cancer, self-assembles into virus-like particles (VLPs) when expressed heterologously. We report the development of a biotechnology platform for HPV16 L1 protein expression based on the constitutivePGK1promoter (PPGK1) from the methylotrophic yeastPichia pastoris. The L1 gene was cloned under regulation ofPPGK1into pPGKΔ3 expression vector to achieve intracellular expression. In parallel, secretion of the L1 protein was obtained through the use of an alternative vector called pPGKΔ3α, in which a codon optimizedα-factor signal sequence was inserted. We devised a work-flow based on the detection of the L1 protein by dot blot, colony blot, and western blot to classify the positive clones. Finally, intracellular HPV VLPs assembly was demonstrated for the first time in yeast cells. This study opens up perspectives for the establishment of an innovative platform for the production of HPV VLPs or other viral antigens for vaccination purposes, based on constitutive expression inP. pastoris.
Optical Spatial Filter to Suppress Beam Wander and Spatial Noise Induced by Atmospheric Turbulence in Free-Space Optical Communications
Authors: Darusalam Ucuk , Priambodo Purnomo Sidi , Rahardjo Eko Tjipto
Published: May 2015

We propose an optical spatial filter (OSF) method to suppress beam wander and spatial noise effects. Signal from random displacements of the focus spot around the optical axis within the constricted area is collected. This method advantageously suppresses fluctuations in signal intensity. The OSF consists of a pinhole and cone reflector. The pinhole produces Fresnel diffraction on the focus spot. The cone reflector provides directed reflectance onto the pinhole for random focus spot displacements due to beam wander. The calculations of signal power are based on fluctuations of signal intensity that are minimized by the circular aperture function of the pinhole and the cosine of the reflectance angle from the cone reflector. The method is applied to free-space optical communications at a wavelength of 1.55 μm with an atmospheric chamber to provide optical propagation media. Based on calculations, the beam wander angles that can be received by the OSF are from 14.0° to 28.0°. Moreover, based on experiment, the OSF with a pinhole diameter of 20.0 μm and cone reflector diameter of 1.5 mm produces signal power of −15.3 dBm. Both calculations and experiment show that the OSF enhances the received signal power in the presence of turbulence.
Proteomic Analysis of Estrogen-Mediated Signal Transduction in Osteoclasts Formation
Authors: Xiong Qi , Tang Peifu , Gao Yanpan , Zhang Lihai , Ge Wei
Published: May 2015

Estrogen plays an important role in inhibiting osteoclast differentiation and protecting against bone loss from osteoporosis, especially in postmenopausal women. However, the precise mechanisms underlying the effect of estrogen on osteoclasts are not well known. In the present study, we performed proteomics analysis and bioinformatics analysis to comprehensively compare the differential expression of proteins in receptor activator of nuclear factor-κB ligand RANKL-induced osteoclasts in the presence and absence of estrogen. We identified 6403 proteins, of which 124 were upregulated and 231 were downregulated by estrogen. Bioinformatics analysis showed that estrogen treatment interfered with 77 intracellular pathways, including both confirmed canonical and unconfirmed pathways of osteoclast formation. Our findings validate the inhibitory effect of estrogen on osteoclasts via the promotion of apoptosis and suppression of differentiation and polarization and suggest that estrogen might inhibit osteoclast formation via other pathways, which requires further investigation and verification.
Early Implementation of QbD in Biopharmaceutical Development: A Practical Example
Authors: Zurdo Jesús , Arnell Andreas , Obrezanova Olga , Smith Noel , Gómez de la Cuesta Ramón , Gallagher Thomas R. A. , Michael Rebecca , Stallwood Yvette , Ekblad Caroline , Abrahmsén Lars , Höidén-Guthenberg Ingmarie
Published: May 2015

In drug development, the “onus” of the low R&D efficiency has been put traditionally onto the drug discovery process (i.e., finding the right target or “binding” functionality). Here, we show that manufacturing is not only a central component of product success, but also that, by integrating manufacturing and discovery activities in a “holistic” interpretation of QbD methodologies, we could expect to increase the efficiency of the drug discovery process as a whole. In this new context, early risk assessment, using developability methodologies and computational methods in particular, can assist in reducing risks during development in a cost-effective way. We define specific areas of risk and how they can impact product quality in a broad sense, including essential aspects such as product efficacy and patient safety. Emerging industry practices around developability are introduced, including some specific examples of applications to biotherapeutics. Furthermore, we suggest some potential workflows to illustrate how developability strategies can be introduced in practical terms during early drug development in order to mitigate risks, reduce drug attrition and ultimately increase the robustness of the biopharmaceutical supply chain. Finally, we also discuss how the implementation of such methodologies could accelerate the access of new therapeutic treatments to patients in the clinic.
Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy
Authors: Zhang Duo , Jiang Shuang , Meng Heng
Published: May 2015

Defective cognitive function is common in patients with diabetes, suggesting that insulin normally exerts anabolic actions in neuron, namely, diabetic encephalopathy. However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in most of tissues, such as muscle and bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in the pathogenesis of diabetic encephalopathy. To overcome this problem, we examined insulin signaling and action in primary PC-12 cells engineered for conditional disruption of the IGF-1 receptor (ΔIGF-1R). The results showed that the lower glucose metabolism and high expression of IGF-1R occurred in the brain of the DE rat model. The results also showed the defect of IGF-1R could significantly improve the ability of glucose consumption and enhance sensitivity to insulin-induced IR and Akt phosphorylation in PC12 cells. And meanwhile, IGF-1R allele gene knockout (IGF-1Rneo) mice treated with HFD/STZ had better cognitive abilities than those of wild mice. Those results indicate that insulin exerts direct anabolic actions in neuron-like cells by activation of its cognate receptor and prove that IGF-1R plays an important role in the pathogenesis of diabetic encephalopathy.
Effects of Qili Qiangxin Capsule on AQP2, V2R, and AT1R in Rats with Chronic Heart Failure
Authors: Cui Xiangning , Zhang Jian , Li Yubo , Sun Yuxiu , Cao Jian , Zhao Mingjing , Zhao Yizhou , Zhao Xin , He Yaoyao , Han Anbang
Published: May 2015

Qili qiangxin capsule (QL), a traditional Chinese herbal compound, has been proved to be effective and safe for the treatment of chronic heart failure (CHF). Upregulation of aquaporin-2 (AQP2) accounts for the water retention in CHF. The aim of the present study was to evaluate the effects of QL on the expression of AQP2 in rats with CHF induced by acute myocardial infarction and to investigate the underlying mechanisms. The urine output of all rats was quantified and collected every day at the first week and the 4th week after administration of QL or Valsartan. The expression of AQP2, vasopressin type 2 receptor (V2R), and angiotensin II type 1 receptor (AT1R) were examined after treatment for 4 weeks. Urinary output increased significantly after administration of QL. Importantly, the protein expression of AQP2 and AQP2 phosphorylated at serine 256 (pS256-AQP2) was downregulated after administration of QL and Valsartan to CHF rats. Furthermore, QL reduced plasma arginine vasopressin (AVP) and angiotensin II (AngII) level and downregulated V2R and AT1R protein expression. Thus, QL exerts its diuretic effect and improves cardiac function in CHF rats by reversing the increases in both AQP2 and pS256-AQP2 expression. The possible mechanisms may involve inhibition of V2R and AT1R.
Stability Analysis for Viral Infection Model with Multitarget Cells, Beddington-DeAngelis Functional Response, and Humoral Immunity
Authors: Tian Xinxin , Wang Jinliang
Published: May 2015

We formulate a (2n+2)-dimensional viral infection model with humoral immunity,nclasses of uninfected target cells and  nclasses of infected cells. The incidence rate of infection is given by nonlinear incidence rate, Beddington-DeAngelis functional response. The model admits discrete time delays describing the time needed for infection of uninfected target cells and virus replication. By constructing suitable Lyapunov functionals, we establish that the global dynamics are determined by two sharp threshold parameters:R0andR1. Namely, a typical two-threshold scenario is shown. IfR0≤1, the infection-free equilibriumP0is globally asymptotically stable, and the viruses are cleared. IfR1≤11, the endemic equilibriumP2is globally asymptotically stable, and the infection is chronic with persistent antibody immune response.
Controlled Pore Formation on Mesoporous Single Crystalline Silicon Nanowires: Threshold and Mechanisms
Authors: Weidemann Stefan , Kockert Maximilian , Wallacher Dirk , Ramsteiner Manfred , Mogilatenko Anna , Rademann Klaus , Fischer Saskia F.
Published: May 2015

Silicon nanowires are prepared by the method of the two‐step metal‐assisted wet chemical etching. We analyzed the structure of solid, rough, and porous nanowire surfaces of boron‐doped silicon substrates with resistivities of ρ > 1000 Ωcm, ρ = 14–23 Ωcm, and ρ < 0.01 Ωcm by scanning electron microscopy and nitrogen gas adsorption. Silicon nanowires prepared from highly doped silicon reveal mesopores on their surface. However, we found a limit for pore formation. Pores were only formed by etching below a critical H2O2 concentration ( M). Furthermore, we determined the pore size distribution dependent on the etching parameters and characterized the morphology of the pores on the nanowire surface. The pores are in the regime of small mesopores with a mean diameter of 9–13 nm. Crystal and surface structure of individual mesoporous nanowires were investigated by transmission electron microscopy. The vibrational properties of nanowire ensembles were investigated by Raman spectroscopy. Heavily boron‐doped silicon nanowires are highly porous and the remaining single crystalline silicon nanoscale mesh leads to a redshift and a strong asymmetric line broadening for Raman scattering by optical phonons at 520 cm−1. This redshift, λSi  bulk = 520 cm−1  →λSi  nanowire = 512 cm−1, hints to a phonon confinement in mesoporous single crystalline silicon nanowires.
Compliance Matrix of a Single-Bent Leaf Flexure for a Modal Analysis
Authors: Nguyen Nghia-Huu , Lee Moo-Yeon , Kim Ji-Soo , Lee Dong-Yeon
Published: May 2015

We present a compliance matrix for a single-bent leaf flexure (SBLF) that shows the relationships between the deformations and the six-axis loads applied to the SBLF. Higher-order beam theory that considers the variable shear and warping effect is considered in bending. The partially restrained warping at the junction between elements is also considered in torsion. The total strain energy is calculated, and the complete compliance matrix is derived by using Castigliano’s second theorem. Sensitivity analyses over the compliance elements are performed and verified via finite element analysis (FEA). The results show that the derived compliance elements are in good agreement with FEA, with errors of less than 7.6%. We suggest that theoretical compliance elements considering variable shear and warping in bending and partially restrained warping in torsion give highly accurate design equations representing the compliant mechanism of the SBLF. The present work could be used in a modal analysis of a single-bent leaf flexure.
Expandable Total Humeral Replacement in a Child with Osteosarcoma
Authors: Henderson Eric R. , Gao Jidi , Groundland John , Binitie Odion , Letson G. Douglas
Published: May 2015

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent.Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option.
The J-Domain of Heat Shock Protein 40 Can Enhance the Transduction Efficiency of Arginine-Rich Cell-Penetrating Peptides
Authors: Lin Tzu-Yin , Su Yu-Hsiu , Lee Kun-Hsiung , Chuang Chin-Kai
Published: May 2015

Sense and antisense oligonucleotide pairs encoding cell-penetrating peptides PTD(Tat47–57), DPV3A, E162, pVEC, R11, and TP13 were used to construct two sets of pET22b-CPP-DsRed and pET22b-CPP-J-DsRed vectors for CPP-DsRed and CPP-J-DsRed recombinant proteins expression. PTD-DsRed, DPV3A-DsRed, PTD-J-DsRed, and DPV3A-J-DsRed recombinant proteins were expressed in a soluble form. PTD-J-DsRed and DPV3A-J-DsRed recombinant proteins were able to escape fromE. colihost cells into the culture medium. The membrane-penetrating activity of PTD-J-DsRed and DPV3A-J-DsRed recombinant proteins to mammalian cells was more effective than that of PTD-DsRed and DPV3A-DsRed. The route of the cellular membrane translocation of these recombinant proteins is suggested via macropinocytosis followed by an endosomal escape pathway.
Theoretic Framework and Finite Element Implementation on Progressive Collapse Simulation of Masonry Arch Bridge
Authors: Peng Weibing , Pan Ruodan , Dai Fei
Published: May 2015

The capacity that computer can solve more complex design problem is gradually increased. Progressive collapse simulation of masonry arch bridge needs a breakthrough in the current development limitations and then becomes more accurate and integrated. This paper proposes a theoretic framework and finite element implementation on progressive collapse simulation of masonry arch bridge. It is intended to develop a new large deformation element in OpenSees, which can be used for analyzing the collapse process of masonry arch bridge. A mathematical method for large deformation element is put forward by large deformation element. The feature model for bridge structure allows families of bridge components to be specified using constraints on geometry and topology. Geometric constraints are established in bridge components by feature dependence graph in the feature model for bridge. A bridge collapse simulation software system was developed according to such combined technologies. Results from our implementation show that the method can help to simulate the progressive collapse process of masonry arch bridge.
Caristi’s Fixed Point Theorem and Subrahmanyam’s Fixed Point Theorem inν-Generalized Metric Spaces
Authors: Alamri Badriah , Suzuki Tomonari , Khan Liaqat Ali
Published: May 2015

We discuss the completeness ofν-generalized metric spaces in the sense of Branciari. We also prove generalizations of Subrahmanyam’s and Caristi’s fixed point theorem.