bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling of theBacillus subtilisBacterial Biofilm Growing on an Agar Substrate
Authors: Wang Xiaoling , Wang Guoqing , Hao Mudong
Published: August 2015

Bacterial biofilms are organized communities composed of millions of microorganisms that accumulate on almost any kinds of surfaces. In this paper, a biofilm growth model on an agar substrate is developed based on mass conservation principles, Fick’s first law, and Monod’s kinetic reaction, by considering nutrient diffusion between biofilm and agar substrate. Our results show biofilm growth evolution characteristics such as biofilm thickness, active biomass, and nutrient concentration in the agar substrate. We quantitatively obtain biofilm growth dependence on different parameters. We provide an alternative mathematical method to describe other kinds of biofilm growth such as multiple bacterial species biofilm and also biofilm growth on various complex substrates.
Morphometric Analysis of Human Embryonic Stem Cell-Derived Ventricular Cardiomyocytes: Determining the Maturation State of a Population by Quantifying Parameters in Individual Cells
Authors: Chan Harvey Y. S. , Keung Wendy , Li Ronald A. , Miller Andrew L. , Webb Sarah E.
Published: August 2015

Quantitative methods were established to determine the level of maturation of human embryonic stem cell-derived ventricular cardiomyocytes (hESC-vCMs) that were treated with different metabolic stimulants (i.e., isoproterenol and oleic acid) during early differentiation. Cells were double-immunolabeled withα-actinin and COX IV antibodies, to label the myofibrils and mitochondria, respectively, after which images were acquired via confocal microscopy. In order to determine the extent of differentiation, image analysis protocols were then used to quantify cell shape and area, as well as the degree of myofibrillar organization and intercalation of mitochondria between the myofibrils within the cells. We demonstrated that oleic acid or isoproterenol alone, or a combination of the two, induced a more elongated hESC-vCM phenotype than the untreated controls. In addition, cells treated with isoproterenol alone exhibited a similar level of myofibrillar organization as the controls, but those treated with oleic acid with/without isoproterenol exhibited a more organized (parallel) orientation of myofibrils. The combined isoproterenol/oleic acid treatment also resulted in enhanced intercalation of mitochondria between the myofibrils. We suggest that these quantitative morphometric methods might serve as simple and effective tools that can be utilized in the determination of the level of structural maturation of hESC-vCMs.
Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children
Authors: Esposito Susanna , Principi Nicola
Published: August 2015

Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.
Expression of the Genes Encoding the Trk and Kdp Potassium Transport Systems ofMycobacterium tuberculosisduring GrowthIn Vitro
Authors: Cholo Moloko C. , van Rensburg Elizabeth J. , Osman Ayman G. , Anderson Ronald
Published: August 2015

Two potassium (K+)-uptake systems, Trk and Kdp, are operative inMycobacterium tuberculosis(Mtb), but the environmental factors triggering their expression have not been determined. The current study has evaluated the expression of these genes in theMtbwild-type and atrk-gene knockout strain at various stages of logarithmic growth in relation to extracellular K+concentrations and pH. In both strains, mRNA levels of the K+-uptake encoding genes were relatively low compared to those of the housekeeping gene,sigA, at the early- and mid-log phases, increasing during late-log. Increased gene expression coincided with decreased K+uptake in the context of a drop in extracellular pH and sustained high extracellular K+concentrations. In an additional series of experiments, the pH of the growth medium was manipulated by the addition of 1N HCl/NaOH. Decreasing the pH resulted in reductions in both membrane potential and K+uptake in the setting of significant induction of genes encoding both K+transporters. These observations are consistent with induction of the genes encoding the active K+transporters ofMtbas a strategy to compensate for loss of membrane potential-driven uptake of K+at low extracellular pH. Induction of these genes may promote survival in the acidic environments of the intracellular vacuole and granuloma.
Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women
Authors: Mondragón-Ceballos Ricardo , García Granados Mónica Dafne , Cerda-Molina Ana Lilia , Chavira-Ramírez Roberto , Hernández-López Leonor Estela
Published: August 2015

We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs) and body mass indices (BMIs). Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (b±s.e.=-0.000003±0.000001; t94=-2.12, adjusted R2=-0.008, P=0.03). Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days.
Convergence Insufficiency/Divergence Insufficiency Convergence Excess/Divergence Excess: Some Facts and Fictions
Authors: Khawam Edward , Abiad Bachir , Boughannam Alaa , Saade Joanna , Alameddine Ramzi
Published: August 2015

Great discrepancies are often encountered between the distance fixation and the near-fixation esodeviations and exodeviations. They are all attributed to either anomalies of the AC/A ratio or anomalies of the fusional convergence or divergence amplitudes. We report a case with pseudoconvergence insufficiency and another one with pseudoaccommodative convergence excess. In both cases, conv./div. excess and insufficiency were erroneously attributed to anomalies of the AC/A ratio or to anomalies of the fusional amplitudes. Our purpose is to show that numerous factors, other than anomalies in the AC/A ratio or anomalies in the fusional conv. or divergence amplitudes, can contaminate either the distance or the near deviations. This results in significant discrepancies between the distance and the near deviations despite a normal AC/A ratio and normal fusional amplitudes, leading to erroneous diagnoses and inappropriate treatment models.
Prognostic Role of MicroRNA-126 for Survival in Malignant Tumors: A Systematic Review and Meta-Analysis
Authors: Bu Jie , Li Hui , Li Xiao-yang , Liu Li-hong , Sun Wei , Xiao Tao
Published: August 2015

Background.Increasing studies found that miR-126 expression may be associated with the prognosis of cancers. Here, we performed a meta-analysis to assess the prognostic role of miR-126 in different cancers.Methods.Eligible studies were identified by searching in PubMed, Embase, the Cochrane Library, CNKI, and Wan Fang databases up to March 2015. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to investigate the correlation between miR-126 and survival of cancers.Results.Thirty studies including a total of 4497 participants were enrolled in this meta-analysis. The pooled results showed that high level of miR-126 was a predictor for favorable survival of carcinomas, with pooled HR of 0.77 (95% CI 0.64–0.93) for OS, 0.64 (95%CI 0.48–0.85) for DFS, and 0.70 (95% CI 0.50–0.98) for PFS/RFS/DSS. However, high level of circulating miR-126 predicted a significantly worse OS in patients with cancer (HR = 1.65, 95% CI 1.09–2.51).Conclusions.Our results indicated that miR-126 could act as a significant biomarker in the prognosis of various cancers.
Purple Urine Bag Syndrome in Two Elderly Men with Urinary Tract Infection
Authors: Van Keer Jan , Detroyer Daan , Bammens Bert
Published: August 2015

Purple urine bag syndrome is a rare condition in which purple discoloration of urine inside its collection bag occurs. We describe two illustrative cases. The first patient is an 81-year-old man who was hospitalized for a newly diagnosed lymphoma with acute obstructive renal failure for which a nephrostomy procedure was performed. During the hospitalization, a sudden purple discoloration of the suprapubic catheter urine was noted, while the nephrostomy urine had a normal color. Urine culture from the suprapubic catheter was positive forPseudomonas aeruginosaandEnterococcus faecalis; urine from the nephrostomy was sterile. The second case is an 80-year-old man who was admitted for heart failure with cardiorenal dilemma and who was started on intermittent hemodialysis. There was a sudden purple discoloration of the urine in the collection bag from his indwelling catheter. He was diagnosed with anE. coliurinary infection and treated with amoxicillin and removal of the indwelling catheter. These two cases illustrate the typical characteristics of purple urine bag syndrome.
A Coupled User Clustering Algorithm Based on Mixed Data for Web-Based Learning Systems
Authors: Niu Ke , Niu Zhendong , Su Yan , Wang Can , Lu Hao , Guan Jian
Published: August 2015

In traditional Web-based learning systems, due to insufficient learning behaviors analysis and personalized study guides, a few user clustering algorithms are introduced. While analyzing the behaviors with these algorithms, researchers generally focus on continuous data but easily neglect discrete data, each of which is generated from online learning actions. Moreover, there are implicit coupled interactions among the data but are frequently ignored in the introduced algorithms. Therefore, a mass of significant information which can positively affect clustering accuracy is neglected. To solve the above issues, we proposed a coupled user clustering algorithm for Wed-based learning systems by taking into account both discrete and continuous data, as well as intracoupled and intercoupled interactions of the data. The experiment result in this paper demonstrates the outperformance of the proposed algorithm.
Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis
Authors: Lee Sang Hoon , Park Moo Suk , Park Byung Hoon , Jung Won Jai , Lee In Seon , Kim Song Yee , Kim Eun Young , Jung Ji Ye , Kang Young Ae , Kim Young Sam , Kim Se Kyu , Chang Joon , Chung Kyung Soo
Published: August 2015

Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations.Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7.Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043,p=0.020,p=0.005, andp=0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018andp=0.008, resp.).Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.
Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice
Authors: Hou Shaocong , Li Caina , Huan Yi , Liu Shuainan , Liu Quan , Sun Sujuan , Jiang Qian , Jia Chunming , Shen Zhufang
Published: August 2015

Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increasedβ-cell area, improved islet morphology, and reducedβ-cell apoptosis. In accordance with the promotion ofβ-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promotingβ-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes.
Quantifying Poincare’s Continuation Method for Nonlinear Oscillators
Authors: Núñez Daniel , Rivera Andrés
Published: August 2015

In the sixties, Loud obtained interesting results of continuation on periodic solutions in driven nonlinear oscillators with small parameter (Loud, 1964). In this paper Loud’s results are extended out for periodically driven Duffing equations with odd symmetry quantifying the continuation parameter for a periodic odd solution which is elliptic and emanates from the equilibrium of the nonperturbed problem.
MATLAB User Interface for Simulation of Silicon Germanium Solar Cell
Authors: Singh Ashish Kumar , Tiwari Jahnvi , Yadav Ashish , Jha Rakesh Kumar
Published: August 2015

Nuclear fusion reaction on the sun is the largest source of energy. In this paper, qualitative investigation of the numerical model of silicon germanium heterojunction solar cell is performed using MATLAB graphical user interface. The heterostructure is designed as Si1-xGex for speculative determination of appropriate germanium mole fraction to get the maximized thin-film solar cell efficiency (ή). Other characteristics such as absorption coefficient (α), energy band gap (EgSiGe), reflectivity (r), open circuit voltage (Voc), and generation rate (Gλ,x) are also considered. This user interface will reduce the complexity of solving differential equation for the analysis of silicon germanium heterojunction cell.
Synthesis and Optical Characterization of Europium Doped MY2O4 (M = Mg, Ca, and Sr) Nanophosphors for Solid State Lightening Applications
Authors: Singh Devender , Tanwar Vijeta , Bhagwan Shri , Nishal Vandna , Sheoran Suman , Kadyan Sonika , Samantilleke Anura P. , Kadyan Pratap Singh
Published: August 2015

Trivalent europium doped yttriate nanophosphors were synthesized by rapid facile gel combustion technique. The photoluminescence (PL) properties of these Eu3+ activated MY2O4 (M = Mg, Ca, and Sr) nanophosphors showed red luminescence and exhibited excellent emission properties in their respective regions of color coordinates. Based on the excitation wavelengths multiple emission peaks were obtained. The main peak in the emission spectra was ascribed to 5D0→7F2 transition of Eu3+ ion. The structural and morphological studies were performed by the measurements of X-ray diffraction profiles, scanning electron microscope (SEM) images, and transmission electron microscope (TEM) micrographs. Furthermore, the effects of additional heating on the different host lattices of these phosphors were also studied.
Improved Secret Image Sharing Scheme in Embedding Capacity without Underflow and Overflow
Authors: Pang Liaojun , Miao Deyu , Li Huixian , Wang Qiong
Published: August 2015

Computational secret image sharing (CSIS) is an effective way to protect a secret image during its transmission and storage, and thus it has attracted lots of attentions since its appearance. Nowadays, it has become a hot topic for researchers to improve the embedding capacity and eliminate the underflow and overflow situations, which is embarrassing and difficult to deal with. The scheme, which has the highest embedding capacity among the existing schemes, has the underflow and overflow problems. Although the underflow and overflow situations have been well dealt with by different methods, the embedding capacities of these methods are reduced more or less. Motivated by these concerns, we propose a novel scheme, in which we take the differential coding, Huffman coding, and data converting to compress the secret image before embedding it to further improve the embedding capacity, and the pixel mapping matrix embedding method with a newly designed matrix is used to embed secret image data into the cover image to avoid the underflow and overflow situations. Experiment results show that our scheme can improve the embedding capacity further and eliminate the underflow and overflow situations at the same time.
Micro-Doppler Ambiguity Resolution Based on Short-Time Compressed Sensing
Authors: Zhuang Jing-bo , Deng Zhen-miao , Ye Yi-shan , Zhang Yi-xiong , Chen Yan-yong
Published: August 2015

When using a long range radar (LRR) to track a target with micromotion, the micro-Doppler embodied in the radar echoes may suffer from ambiguity problem. In this paper, we propose a novel method based on compressed sensing (CS) to solve micro-Doppler ambiguity. According to the RIP requirement, a sparse probing pulse train with its transmitting time random is designed. After matched filtering, the slow-time echo signals of the micromotion target can be viewed as randomly sparse sampling of Doppler spectrum. Select several successive pulses to form a short-time window and the CS sensing matrix can be built according to the time stamps of these pulses. Then performing Orthogonal Matching Pursuit (OMP), the unambiguous micro-Doppler spectrum can be obtained. The proposed algorithm is verified using the echo signals generated according to the theoretical model and the signals with micro-Doppler signature produced using the commercial electromagnetic simulation software FEKO.
Security Enhancement Using Cache Based Reauthentication in WiMAX Based E‐Learning System
Authors: Rajagopal Chithra , Bhuvaneshwaran Kalaavathi
Published: August 2015

WiMAX networks are the most suitable for E‐Learning through their Broadcast and Multicast Services at rural areas. Authentication of users is carried out by AAA server in WiMAX. In E‐Learning systems the users must be forced to perform reauthentication to overcome the session hijacking problem. The reauthentication of users introduces frequent delay in the data access which is crucial in delaying sensitive applications such as E‐Learning. In order to perform fast reauthentication caching mechanism known as Key Caching Based Authentication scheme is introduced in this paper. Even though the cache mechanism requires extra storage to keep the user credentials, this type of mechanism reduces the 50% of the delay occurring during reauthentication.
In VitroComparison of Dynesys, PEEK, and Titanium Constructs in the Lumbar Spine
Authors: Yeager Matthew S. , Cook Daniel J. , Cheng Boyle C.
Published: August 2015

Introduction. Pedicle based posterior dynamic stabilization systems aim to stabilize the pathologic spine while also allowing sufficient motion to mitigate adjacent level effects. Two flexible constructs that have been proposed to act in such a manner, the Dynesys Dynamic Stabilization System and PEEK rod, have yet to be directly comparedin vitroto a rigid Titanium rod.Methods. Human lumbar specimens were tested in flexion extension, lateral bending, and axial torsion to evaluate the following conditions at L4-L5: Intact, Dynesys, PEEK rod, Titanium rod, and Destabilized. Intervertebral range of motion, interpedicular travel, and interpedicular displacement metrics were evaluated from 3rd-cycle data using an optoelectric tracking system.Results. Statistically significant decreases in ROM compared to Intact and Destabilized conditions were detected for the instrumented conditions during flexion extension and lateral bending. AT ROM was significantly less than Destabilized but not the Intact condition. Similar trends were found for interpedicular displacement in all modes of loading; however, interpedicular travel trends were less consistent. More importantly, no metrics under any mode of loading revealed significant differences between Dynesys, PEEK, and Titanium.Conclusion. The results of this study support previous findings that Dynesys and PEEK constructs behave similarly to a Titanium rodin vitro.
Feasibility of Comparing the Results of Pancreatic Resections between Surgeons: A Systematic Review and Meta-Analysis of Pancreatic Resections
Authors: Gurusamy Kurinchi , Toon Clare , Virendrakumar Bhavisha , Morris Steve , Davidson Brian
Published: August 2015

Background.Indicators of operative outcomes could be used to identify underperforming surgeons for support and training. The feasibility of identifying HPB surgeons with poor operative performance (“outliers”) based on the results of pancreatic resections is not known.Methods.A systematic review of Medline, Embase, and the Cochrane library was performed to identify studies on pancreatic resection including at least 100 patients and published between 2004 and 2014. Proportions that lay outside the upper 95% and 99.8% confidence intervals based on results of the systematic reviews were considered as “outliers.”Results.In total, 30 studies reporting on 10712 patients were eligible for inclusion in this review. The average short-term mortality after pancreatic resections was 3.1% and proportion of patients with procedure-related complications was 47.0%. None of the classification systems assessed the long-term impact of the complications on patients. The surgeon-specific mortality should be 5 times the average mortality before he or she can be identified as an outlier with 0.1% false positive rate if he or she performs 50 surgeries a year.Conclusions.A valid risk prognostic model and a classification system of surgical complications are necessary before meaningful comparisons of the operative performance between pancreatic surgeons can be made.
ESBLE. coliUrosepsis Resulting in Endogenous Panophthalmitis Requiring Evisceration of the Eye in a Diabetic Patient
Authors: Arunachala Murthy Tejaswini , Rangappa Pradeep , Rao Sangeetha , Rao Karthik
Published: August 2015

A primary infection in a remote site resulting in vision threatening complications like panophthalmitis in a person who is not immune-compromised is rare. We report a case of endogenous bilateral bacterial endophthalmitis progressing into panophthalmitis in one eye requiring evisceration of that eye. A patient admitted with severe ESBLE. coliurosepsis was effectively treated with source control (bilateral DJ stenting for hydroureteronephrosis) and antibiotics. She was found to have features suggestive of bilateral conjunctivitis which progressed to panophthalmitis possibly due to delay in appropriate diagnosis and treatment. Diagnosis requires a very high index of suspicion if eye involvement is noted in a patient with features of bacteraemia and early intervention could possibly produce better outcomes. To our knowledge, this is the first case of ESBLE. coliurosepsis complicated by microbiologically confirmed panophthalmitis.
Female Sex Hormones Pattern and Its Relation to Disease Severity and Treatment in Pre- and Postmenopausal Patients with Chronic Hepatitis C Virus (Genotype 4) Infection
Authors: Ahmed Nora H. , El-Abaseri Taghrid B. , El-Sayed Hesham F. , El-Serafi Taher I.
Published: August 2015

Chronic hepatitis C (CHC) course revealed differences between men and women. Male gender and postmenopausal women are thought to be of the critical factors affecting HCV infection progression. The study aimed to assess female sex hormones and their relation to disease severity and treatment in HCV infected females. Subjects were divided to 2 groups: 44 CHC female patients and 44 controls. Both groups were classified to premenopausal and postmenopausal females. Serum estradiol (E2), progesterone (PRG), and total testosterone (TT) were assessed using chemiluminescent immunoassay. Our results showed that menopausal patients had significantly higher levels of estradiol, total testosterone, and progesterone compared to controls (P<0.001). Reproductive aged patients had lower level of total testosterone compared to menopausal patients (P<0.001). HCV infected females of reproductive age had higher level of progesterone compared to menopausal HCV infected females (P=0.0014). Indicators of disease severity and treatment response were significantly worse in menopausal women compared to reproductive aged women (fibrosis:P<0.001, activity:P=0.045, and treatment:P<0.001). We observed that lower estradiol level may be related to fibrosis severity in CHC females. Higher total testosterone and progesterone levels may be related to fibrosis severity and poor response to treatment in CHC menopausal females only.
Cyclic Strain Enhances Cellular Uptake of Nanoparticles
Authors: Hu Jia , Liu Yaling
Published: August 2015

Nanoparticles (NPs) have gained increasing interest in recent years due to their potential use as drug carrier, imaging, and diagnostic agents in pharmaceutical and biomedical applications. While many cells in vivo experience mechanical forces, little is known about the correlation of the mechanical stimulation and the internalization of NPs into cells. This paper investigates the effects of applied cyclic strain on NP uptake by cells. Bovine aortic endothelial cells (BAECs) were cultured on collagen‐coated culture plates and placed under cyclic equal‐axial strains. NPs of sizes ranging from 50 to 200 nm were loaded at a concentration of 0.02 mg/mL and cyclic strains from 5 to 15% were applied to the cells for one hour. The cyclic strain results in a significant enhancement in NP uptake, which increases almost linearly with strain level. The enhanced uptake also depends on size of the NPs with the highest uptake observed on 100 nm NP. The effect of enhanced NP uptake lasts around 13 hours after cyclic stretch. Such in vitro cell stretch systems mimic physiological conditions of the endothelial cells in vivo and could potentially serve as a biomimetic platform for drug therapeutic evaluation.
Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy
Authors: Vandergriff Adam C. , de Andrade James Bizetto Meira , Tang Junnan , Hensley M. Taylor , Piedrahita Jorge A. , Caranasos Thomas G. , Cheng Ke
Published: August 2015

Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.
Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa
Authors: Tchelougou Daméhan , Kologo Jonas K. , Karou Simplice D. , Yaméogo Valentin N. , Bisseye Cyrille , Djigma Florencia W. , Ouermi Djeneba , Compaoré Tegwindé R. , Assih Maléki , Pietra Virginio , Zabsonré Patrice , Simpore Jacques
Published: August 2015

Objective.This study aimed to investigate the association between three polymorphisms of renin-angiotensin system and the essential hypertension in the population of Burkina Faso.Methodology.This was a case-control study including 202 cases and 204 matched controls subjects. The polymorphisms were identified by a classical and a real-time PCR.Results.The AGT 235M/T and AT1R 1166A/C polymorphisms were not associated with the hypertension while the genotype frequencies of the ACE I/D polymorphism between patients and controls (DD: 66.83% and 35.78%, ID: 28.22% and 50.98%, II: 4.95% and 13.24%, resp.) were significantly different (p< 10−4). The genotype DD of ACE gene (OR = 3.40,p< 0.0001), the increasing age (OR = 3.83,p< 0.0001), obesity (OR = 4.84,p< 0.0001), dyslipidemia (OR = 3.43,p= 0.021), and alcohol intake (OR = 2.76,p< 0.0001) were identified as the independent risk factors for hypertension by multinomial logistic regression.Conclusion.The DD genotype of the ACE gene is involved in susceptibility to hypertension. Further investigations are needed to better monitor and provide individualized care for hypertensive patients.
Induction of Regulatory B-Cells by Mesenchymal Stem Cells is Affected by SDF-1α-CXCR7
Authors: Qin Yan , Zhou Zhihua , Zhang Fang , Wang Yong , Shen Bing , Liu Yong , Guo Yifeng , Fan Yu , Qiu Jianxin
Published: August 2015

Background/Aims: Mesenchymal stem cells (MSCs) possess immunomodulatory properties on a diverse array of immune cell lineages, including regulatory T and B cells (Tregs and Bregs, respectively). However, their specific effects and mechanisms underlying induction of Bregs remain unclear. The immune regulatory function of MSCs is exerted through both cell-cell contact and the release of soluble factors. The main objective of this study was to examine the role of the SDF-1-CXCR4/CXCR7 axis in the secretory action of MSCs, and potential effects on the immunoregulatory function of these cells. Methods: MSCs were isolated from mouse bone marrow and characterized according to their multilineage differentiation potential and their surface antigen expression. CD19+ B cells purified from mice splenocytes were co-cultured with MSCs at various ratios in the presence of LPS and αCD40. After 4 days, intracellular IL-10 production and cell surface CD1d and CD5 expression by CD19+ B cells were determined using flow cytometry, and the secretion of IL-10, IL-6, IgM, and IgG were assessed with ELISA. MSCs were treated with different concentrations of stromal derived factor-1α (SDF-1α) stimuli or transiently overexpressed with CXCR7. and their cell viability and immune regulatory effects of MSCs on Bregs were assessed. Results: MSCs induced IL-10-producing regulatory B cells and primarily stimulated the CD1d+CD5+B cell subset of IL-10+Breg cells to express IL-10. IL-10, IL-6, and IgM secretion were additionally induced by MSCs. The CXCR7 pathway was required for MSC viability and the production of paracrine factors under SDF-1α culture condition. Low concentrations of SDF-1α promoted the immunomodulatory effect of MSCs, leading to a further increase in IL-10-producing regulatory B cells and IL-10 secretion. In contrast, high concentrations of SDF-1α inhibited MSCs induction of IL-10+Breg cells. Notably, CXCR7 overexpression in MSCs reversed the inhibitory effect of high concentrations of SDF-1α and promoted the immunomodulatory effect of these cells. Conclusion: MSCs induce IL-10+Breg cells, which contribute to the generation of an immunosuppressive environment. SDF-1α and its receptor, CXCR7 play important roles in the immunomodulatory function of MSCs by regulating their paracrine actions.
Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure
Authors: Calabrò Salvatrice , Alzoubi Kousi , Faggio Caterina , Laufer Stefan , Lang Florian
Published: August 2015

Background/Aims: The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i), energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofuorescein diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit. Results: A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml) significantly increased the percentage of annexin-V-binding cells (to 9.3 ±0.9 %) and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca2+]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM) and SB203580 (2 µM). Conclusions: Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.
Lithium Chloride Modulates Adipogenesis and Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Tang Linjun , Chen Yu , Pei Fuxing , Zhang Hui
Published: August 2015

Background/Aims: Lithium chloride (LiCl) has long been used as a psychiatric medication; however, its role in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains largely unknown. The aim of this study is to explore the effect of LiCl on the differentiation of BMSCs. Methods: The roles of LiCl in osteogenic and adipogenic processes were observed using alizarin red staining and oil red O staining, respectively. The effects of LiCl on the Wnt and Hedgehog (Hh) pathways were investigated. Results: Our data showed that LiCl effectively promoted osteogenesis and inhibited adipogenesis by simultaneously affecting the Wnt and Hh pathways. Conclusion: These results suggest that LiCl influences the differentiation of BMSCs directly through the Wnt and Hh pathways and thus may be a candidate drug for the treatment of osteoporosis.
Psychological Stress-Derived Prolactin Modulates Occludin Expression in Vaginal Epithelial Cells to Compromise Barrier Function
Authors: Li Xueyan , Liu Xiaowei , Yu Song
Published: August 2015

Background/Aims: The causative factors of the vaginitis are not fully understood yet. Epithelial barrier dysfunction plays a critical role in the pathogenesis of vaginitis. This study aims to investigate the role of prolactin (PRL) in the causing the vaginal epithelial barrier dysfunction. Methods: Adult rats were treated with water-avoid-stress. The serum levels of PRL were determined by ELISA. T84 cell (T84 cells; a vaginal epithelial cell line) monolayers were prepared to be used assessing the epithelial barrier functions. The expression of occludin in T84 cells was assessed by Chromatin immunoprecipitation assay, methylation specifIc PCR, real time quantitative RT-PCR and Western blotting. Results: The results showed that psychological stress markedly increased the serum levels of PRL in the rat vaginal epithelia. Exposure of T84 cells to PRL in the culture markedly increased the phosphorylation of STAT3 and suppressed the expression of occludin in the cells; the transepithelial electric resistance was decreased and the permeability to a macromolecular tracer was increased in the T84 monolayers, which was mimicked by blocking STAT3, or abolished by over expression of occludin in the epithelial cells. Conclusions: Psychological stress-derived PRL induces vaginal epithelial barrier dysfunction by inhibiting the expression of occludin.
NSCLC without Antineoplastic Treatment: Incidence, Characteristics, and Outcome as Outlined in the TYROL Study
Authors: Kocher Florian , Lunger Fabian , Pircher Andreas , Hilbe Wolfgang , Fiegl Michael
Published: August 2015

Background: The treatment of non-small cell lung cancer (NSCLC) has become more and more individualized with the availability of potent and less toxic therapies. However, there are still patients who do not receive antineoplastic treatment. The aim of this study was to investigate the incidence of ‘no treatment', its reasons, and the outcome of untreated NSCLC patients in recent years. Patients and Methods: Medical files of 1,256 consecutive NSCLC patients diagnosed between 2001 and 2009 at the Medical University of Innsbruck and affiliated hospitals were retrospectively analyzed. Results: In 66 of the 1,256 patients (5.3%), the absence of antineoplastic treatment could be ascertained. The median age was 72.1 years, and 42 patients (63.3%) were males. The majority of patients presented with stage IV (n = 45; 68.2%). Treatment was omitted due to physical deterioration in 41 patients (62.1%), and 25 patients (37.9%) refused any treatment. The median overall survival of the untreated patients was 3.1 months (refusal: 9.7 months; physical deterioration: 2.1 months). Conclusion: This study provides information on the incidence of NSCLC patients without antineoplastic treatment and gives a detailed description of the characteristics and comorbidities. These data might help clinicians in the survival estimations of their NSCLC patients in scenarios like therapy refusal or poor physical condition.
Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β1 in a Chronic Mouse Model of Allergic Asthma
Authors: Ram Arjun , Mabalirajan Ulaganathan , Jaiswal Ashish , Rehman Rakhshinda , Singh Vijay Pal , Ghosh Balaram
Published: August 2015

Background: Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial ﬁbrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study. Methods: PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β1 (TGF-β1) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections. Results: Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial ﬁbrosis and elevated TGF-β1, along with significant AHR. PBPB attenuated subepithelial ﬁbrosis with a reduction of lung TGF-β1, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs. Conclusion: Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial ﬁbrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.
Pulmonary Function Test Abnormalities in Pediatric Inflammatory Bowel Disease
Authors: Furlano Raoul I. , Basek Pavel , Müller Pascal , Bieli Christian , Braegger Christian P. , Barben Jürg , Hammer Jürg , Moeller Alexander , Trachsel Daniel
Published: August 2015

Background: Pulmonary involvement in adult patients with inflammatory bowel disease (IBD) seems more common than previously appreciated. Its prevalence and development over time in pediatric IBD patients are largely unknown. Objectives: The aim was to study lung function including fraction of exhaled nitric oxide (FeNO) and transfer capacity for carbon monoxide (TLCO) in pediatric IBD patients and to describe the longitudinal development in a subset of patients with lung function abnormalities. Methods: Sixty-six measurements were made in 48 IBD patients (30 patients with Crohn's disease and 18 with ulcerative colitis) and 108 matched controls. Patients with abnormal TLCO or elevated residual volume/total lung capacity (RV/TLC) ratios were invited for a follow-up. Statistical comparisons were made by nonparametric tests and ANOVA. Results: TLCO was decreased in IBD patients [median: 88% predicted (interquartile range, IQR, 22) vs. 99% predicted (IQR 19) in controls]. RV/TLC ratios were mildly elevated in patients with ulcerative colitis [32% (IQR 9) vs. 27% (IQR 8) in controls], and maximum expiratory flows at 50 and 25% of vital capacity were mildly reduced in patients with Crohn's disease. FeNO and disease activity did not correlate with lung function abnormalities. Abnormalities did not consistently persist over a median follow-up period of 34 months. Conclusions: This study supports evidence that variable and fluctuating pulmonary involvement also occurs in pediatric IBD patients. Its clinical significance is unclear.
Effect of Montelukast Monotherapy on Oxidative Stress Parameters and DNA Damage in Children with Asthma
Authors: Dilek Fatih , Ozkaya Emin , Kocyigit Abdurrahim , Yazici Mebrure , Kesgin Siddika , Gedik Ahmet Hakan , Cakir Erkan
Published: August 2015

Background: There is ample knowledge reported in the literature about the role of oxidative stress in asthma pathogenesis. It is also known that the interaction of reactive oxygen species with DNA may result in DNA strand breaks. The aim of this study was to investigate if montelukast monotherapy affects oxidative stress and DNA damage parameters in a population of pediatric asthma patients. Methods: Group I consisted of 31 newly diagnosed asthmatic patients not taking any medication, and group II consisted of 32 patients who had been treated with montelukast for at least 6 months. Forty healthy control subjects were also enrolled in the study. Plasma total oxidant status (TOS) and total antioxidant status (TAS) were measured to assess oxidative stress. DNA damage was assessed by means of alkaline comet assay. Results: The patients in both group I and group II had statistically significant higher plasma TOS (13.1 ± 4 and 11.1 ± 4.1 μmol H2O2 equivalent/liter, respectively) and low TAS levels (1.4 ± 0.5 and 1.5 ± 0.5 mmol Trolox equivalent/liter, respectively) compared with the control group (TOS: 6.3 ± 3.5 μmol H2O2 equivalent/liter and TAS: 2.7 ± 0.6 mmol Trolox equivalent/liter; p < 0.05). DNA damage was 18.2 ± 1.0 arbitrary units (a.u.) in group I, 16.7 ± 8.2 a.u. in group II and 13.7 ± 3.4 a.u. in the control group. There were statistically significant differences only between group I and the control group (p < 0.05). Conclusions: According to the findings, montelukast therapy makes only minimal but not statistically significant improvement in all TOS, TAS and DNA damage parameters.
Hair Breakage in Patients of African Descent: Role of Dermoscopy
Authors: Quaresma Maria Victória , Martinez Velasco María Abril , Tosti Antonella
Published: August 2015

Dermoscopy represents a useful technique for the diagnosis and follow-up of hair and scalp disorders. To date, little has been published regarding dermoscopy findings of hair disorders in patients of African descent. This article illustrates how dermoscopy allows fast diagnosis of hair breakage due to intrinsic factors and chemical damage in African descent patients.
Antiperistaltic Side-to-Side Ileorectal Anastomosis Is Associated with a Better Short-Term Fecal Continence and Quality of Life in Slow Transit Constipation Patients
Authors: Chen Wei , Jiang C.-Qing , Qian Qun , Ding Zao , Liu Zhi-Su
Published: August 2015

Background: Surgical treatment of refractory slow transit constipation (STC) is traditionally performed using end-to-side ileorectal anastomosis (SE-IRA) with total abdominal colectomy (TAC). Antiperistaltic side-to-side (SS) IRA is suggested to be a superior approach. Employing a well-characterized cohort of STC patients, we compared the postoperative outcomes of the 2 surgical approaches. Methods: A total of 42 patients underwent TAC for refractory idiopathic STC. Twenty patients were treated using traditional SE-IRA whereas 22 patients were treated using SS-IRA. Patients were evaluated at 3 and 6 months as well as at 1 and 2 years after surgery. Both groups were compared for patient characteristics, perioperative data and quality of life. Cleveland Clinic Incontinence Score (CCIS) and Gastrointestinal Quality of Life Index (GQILI) were adopted for evaluating postoperative recovery. Results: Both study groups were comparable with respect to general patient characteristics, disease severity and post-operative complications. Fewer than 30% of all patients reported substantial dissatisfaction with surgical outcomes in both the groups. The SS-IRA group was associated with a lower postoperative CCIS (p < 0.05) and a better GQILI (p < 0.05) than that of the SE-IRA group during early follow-up examinations. Conclusion: In this study, SS-IRA was superior to traditional SE-IRA for the treatment of STC with respect to post-operative outcomes, and especially during early follow-up.
Proteinuria in Patients with Solid Tumors Treated with Ramucirumab: A Systematic Review and Meta-Analysis
Authors: Abdel-Rahman Omar , ElHalawani Hesham
Published: August 2015

Background: We performed a systematic review and meta-analysis of the risk of proteinuria associated with ramucirumab. Methods: Eligible studies included randomized phase II and III trials of patients with solid tumors on ramucirumab, describing events of all-grade and high-grade proteinuria. Results: Our search strategy yielded 170 potentially relevant citations from PubMed/Medline, CENTRAL Cochrane database, ASCO and ESMO meeting libraries. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The relative risk (RR) of all-grade proteinuria was 3.31 (95% CI 2.48-4.42; p < 0.00001). Moreover, the RR of high-grade proteinuria was 5.28 (95% CI 2.32-12.01; p < 0.0001). Conclusions: Our meta-analysis has demonstrated that ramucirumab use is associated with an increased risk of all-grade and high-grade proteinuria. Early detection strategies should be employed in those patients to prevent the progression to more sinister renal disease.