bluuebunny/crossref_metadata_2025 huggingface dataset:
Torsion Dependence of Domain Transition and MI Effect of Melt-Extracted Co68.15Fe4.35Si12.25B13.25Nb1Cu1Microwires
Authors: Xing Dawei , Chen Dongming , Liu Fang , Liu Jingshun , Shen Hongxian , Ning Zhiliang , Cao Fuyang , Sun Jianfei
Published: April 2015

We present the torsional stress induced magnetoimpedance (MI) effect and surface domain structure evolution of magnetostrictive melt-extracted Co68.15Fe4.35Si12.25B13.25Nb1Cu1microwires. Experimental results indicate that the surface domain structures observed by magnetic force microscope (MFM) transform from the weak circumferential domain of as-cast state to the helical domain under large torsional strain of 81.6 (2π rad/m). Domain wall movement distorts at torsional strainξ=20.4(2π rad/m) and forms a helical anisotropy with an angle of around 30° versus axial direction of wire. At 15 MHz, the maximum of GMI ratioΔZ/Z(%) increases to 194.4% atξ=20.4(2π rad/m) from 116.3% of the as-cast state and then decreases to 134.9% atξ=102.0(2π rad/m). The torsion magnetoimpedance (TMI) ratioΔZ/Zξ(%) is up to 290%. Based on this large torsional strain and high MI ratio, the microwire can be as an referred candidate for high-performance TMI sensor application.
Predictors of HIV/AIDS Related Ocular Manifestations among HIV/AIDS Patients in Felege Hiwot Referral Hospital, Northwest Ethiopia
Authors: Sharew Guadie , Azage Muluken
Published: April 2015

Background. Ocular manifestations in people living with HIV/AIDS are varied and affect almost all the structures of eye leading to visual impairment or blindness. Therefore, the aim of this study was to identify the predictors of HIV related ocular manifestation among ART clinic clients.Methods. Institution based cross-sectional study was employed among ART clients at Felege Hiwot referral hospital, northwest Ethiopia. The study was conducted from 1 January 2013 to 30 January 2013. A total of 369 systematically and randomly selected clients were included in the study. Data were collected using structured questionnaires and ophthalmologic clinical examination. Data were entered and analyzed using SPSS version 16.0. Binary and multivariable logistic regression analyses were computed to identify independent predictors of HIV related ocular manifestation.Results. Twenty-five percent (25.7%) of HIV patients had ocular manifestations. The three most frequent signs were Squamoid Conjuctival growth (26.9%), ophthalmic herpes zoster (22.1%), and Bacterial Conjuctivitis (17.2%). History of eye problem, CD4count, and visual acuity of the eye were the predictors of HIV related ocular manifestation.Conclusion. In this study, a higher proportion of ocular manifestations were detected in HIV/AIDS patients. Visual acuity and CD4counts were the independent predictors of ocular manifestations. This finding gives an insight for policy makers and concerned body to integrate ophthalmic examination in ART clinics to improve the health condition of HIV/ADIS patients.
The Pleiotropic Effects of Vitamin D in Gynaecological and Obstetric Diseases: An Overview on a Hot Topic
Authors: Colonese Francesca , Laganà Antonio Simone , Colonese Elisabetta , Sofo Vincenza , Salmeri Francesca Maria , Granese Roberta , Triolo Onofrio
Published: April 2015

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.
The (Pulsed-Wave) Doppler Fetal Myocardial Performance Index: Technical Challenges, Clinical Applications and Future Research
Authors: Mahajan Aditi , Henry Amanda , Meriki Neama , Hernandez-Andrade Edgar , Crispi Fatima , Wu Linda , Welsh Alec W.
Published: April 2015

Functional cardiovascular assessment is becoming an increasingly important tool in the study of fetal pathology. The myocardial performance index (MPI) is a parameter measuring global myocardial function. Since its introduction, several studies have proposed methods to improve its reproducibility and have constructed normative reference ranges. Fetal heart evaluation using the MPI is technically challenging, requiring specific training and expertise, and a consensus has yet to be reached on the method of delineating the time periods used to calculate the index. Despite these limitations, it has been shown to be a useful and highly sensitive parameter of dysfunction in a number of fetal pathologies. Further research is warranted into the effect of pathology on MPI, parameters of unilateral cardiac strain that utilise MPI, and automation of the MPI to encourage incorporation of the MPI as a useful tool in clinical practice.
In vitro and in vivo Drug-Drug Interaction of Losartan and Glimepiride in Rats and Its Possible Mechanism
Authors: Chen Sai-Zhen , Pan Pei-Pei , Wang Shuang-Hu , Luo Jun , Hu Guo-Xin , Xu Shan-Shan , Zhang Lu , Yu Yin-Fei
Published: April 2015

Background: Losartan and glimepiride are commonly used drugs to treat chronic diseases of hypertension and diabetes; they are both substrates of CYP2C9. The aim of the present study was to investigate the possible interaction of losartan and glimepiride both in vitro (rat liver microsomes) and in vivo (healthy Sprague-Dawley rats). Methods: In rat liver microsomes, 1-10 μmol/l losartan and glimepiride were coincubated, and the inhibitory effect was analyzed. In the subsequent pharmacokinetic study, 15 healthy Sprague-Dawley rats received administrations of 5 mg/kg losartan or 1 mg/kg glimepiride or a coadministration. Results: In the rat liver microsome system, glimepiride showed a slight inhibition of losartan at concentrations of 1-10 μmol/l, whereas losartan exhibited no inhibitory effect on glimepiride. In vivo, glimepiride did not modify the plasma concentration of losartan and its metabolite E-3174. The alteration of an increased AUC and Cmax was observed in the pharmacokinetic parameters of glimepiride and hydroxy glimepiride. Conclusions: Glimepiride did not affect losartan pharmacokinetics in rats, while losartan potently altered glimepiride metabolism; this result was inconsistent with the in vitro outcome. The mechanism requires further investigation. In clinical settings, attention should be paid to the interaction of these two drugs in the human body as well as the possible adverse reactions of glimepiride.
Bacterial Lysate Increases the Percentage of Natural Killer T Cells in Peripheral Blood and Alleviates Asthma in Children
Authors: Lu Yanming , Li Yaqin , Xu Lingyun , Xia Min , Cao Lanfang
Published: April 2015

Aims: To assess the efficacy of conventional treatment combined with bacterial lysate [OM-85 Broncho-Vaxom (BV)] in the prevention of asthma in children as well as its influence on the number of natural killer T (NKT) cells and their cytokine production. Materials and Methods: Sixty children diagnosed with asthma were divided into either a BV-treated group (with oral OM-85 BV) or a conventional inhaled corticosteroid (ICS) group. The numbers of NKT cells and CD4+ NKT cells were measured in the peripheral blood by flow cytometry. The levels of IFN-γ, IL-4, and IL-10 after the blood cells had been cultured with an NKT cell agonist were detected by ELISA. Results: After therapy, asthma attacks were significantly decreased compared with before therapy in both groups. However, after therapy, respiratory tract infections were reduced compared with before therapy in the BV-treated group only. Additionally, the frequency of asthma attacks and use of antibiotics in the BV-treated group were lower than in the ICS group. With BV treatment, the numbers of peripheral blood NKT cells and CD4+ NKT cells were higher after therapy than before therapy. After therapy, the ratio of IFN-γ/IL-4 and IL-10 levels were increased in the BV-treated group, whereas IL-4 was reduced in the BV-treated group compared with the ICS group. Conclusion: BV combined with conventional asthma treatment can prevent recurrent respiratory tract infections and suppress the severity of asthma attacks, possibly by altering the rates and cytokines of NKT cells.
Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study
Authors: Saum Kai-Uwe , Dieffenbach Aida Karina , Jansen Eugène H.J.M. , Schöttker Ben , Holleczek Bernd , Hauer Klaus , Brenner Hermann
Published: April 2015

Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. Objective: In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. Methods: This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Results: Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values <0.0001). Comparing highest and lowest quartiles of the biomarkers, statistically significant positive associations with frailty were observed for d-ROM (OR: 2.02, 95% CI: 1.25-3.25) and CRP (OR: 3.15, 95% CI: 2.00-4.96), respectively, after controlling for age and sex. An inverse statistically significant association with frailty was observed for TTL (OR: 0.42, 95% CI: 0.25-0.69). Conclusion: The strong associations with OS biomarkers and CRP support a major role of OS and inflammation in the development of frailty, which should be followed up in further longitudinal studies on frailty.
Effects of Methoxychlor and 2,2-bis (p-Hydroxyphenyl)-1,1,1-Trichloroethane on Cytochrome P450 Enzyme Activities in Human and Rat Livers
Authors: Chen Bingbing , Pan Peipei , Wang Li , Chen Menchun , Dong Yaoyao , Ge Ren-Shan , Hu Guo-Xin
Published: April 2015

Cytochrome P450 (CYP) enzymes are involved in the metabolism of endogenous and exogenous compounds. Human and rat liver microsomes were used to investigate the inhibitory effects of methoxychlor (MXC) and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on the activities of corresponding human and rat CYPs. Probe drugs were used to test the inhibitory effects of MXC and HPTE on human and rat CYPs. The results showed that MXC and HPTE inhibited both human CYP2C9 and rat liver CYP2C11 activity, with half-maximal inhibitory concentration (IC50) values of 15.47 ± 0.36 (MXC) and 8.87 ± 0.53 μmol/l (HPTE) for human CYP2C9, and of 22.45 ± 1.48 (MXC) and 24.63 ± 1.35 μmol/l (HPTE) for rat CYP2C11. MXC and HPTE had no effects on human CYP2C19 activity but inhibited rat CYP2C6 activity with IC50 values of 14.84 ± 0.04 (MXC) and 8.72 ± 0.25 μmol/l (HPTE). With regard to human CYP2D6 and rat CYP2D2 activity, only HPTE potently inhibited human CYP2D6 activity, with an IC50 value of 16.56 ± 0.69 μmol/l. Both chemicals had no effect on human CYP3A4 and rat CYP3A1 activity. In summary, MXC and HPTE are potent inhibitors of some human and rat CYPs.
A Small Region of Porcine Hemagglutinating Encephalomyelitis Virus Spike Protein Interacts with the Neural Cell Adhesion Molecule
Authors: Dong Bo , Gao Wei , Lu Huijun , Zhao Kui , Ding Ning , Liu Wenfeng , Zhao Jiakuan , Lan Yungang , Tang Bo , Jin Zhao , He Wenqi , Gao Feng
Published: April 2015

Objective: The spike (S) protein of porcine hemagglutinating encephalomyelitis virus (PHEV) may mediate infection by binding to a cellular neural cell adhesion molecule (NCAM). This study aimed to identify the crucial domain of the S1 subunit of the S protein that interacts with NCAM. Methods: Three truncated segments (S1-291, S277-794 and S548-868) of the S gene of PHEV and the NCAM gene were cloned individually into the Escherichia coli expression vectors and yeast two-hybrid expression vectors. The interaction between S1-291, S277-794, S548-868 and NCAM were detected by a GST pull-down experiment and yeast two-hybrid assay. Results: Three fusion proteins (S1-291, S277-794 and S548-868) were screened for their interactions with NCAM by protein-protein interaction assays. The results of these assays clarified that S277-794 interacted with NCAM, while S1-291 and S548-868 did not. Conclusions: A small fragment (258-amino-acid fragment, residues 291-548) on the PHEV S protein was posited to be the minimum number of amino acids necessary to interact with NCAM. This fragment may be the receptor-binding domain that mediates PHEV binding to NCAM.
Advances in Understanding of the Pathogenesis of Acute Respiratory Distress Syndrome
Authors: Sharp Charles , Millar Ann B. , Medford Andrew R.L.
Published: April 2015

The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. The resulting loss of gas exchange leads to acute respiratory failure and typically catastrophic illness, termed acute respiratory distress syndrome (ARDS), requiring ventilatory and critical care support. There remains a significant disease burden, with some estimates showing 200,000 cases each year in the USA with a mortality approaching 50%. In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.
Therapeutic Bronchoscopy Improves Spirometry, Quality of Life, and Survival in Central Airway Obstruction
Authors: Mahmood Kamran , Wahidi Momen M. , Thomas Samantha , Argento Angela Christine , Ninan Neil A. , Smathers Emily C. , Shofer Scott L.
Published: April 2015

Background: Central airway obstruction (CAO) occurs in patients with primary or metastatic lung malignancy and nonmalignant pulmonary disorders and results in significant adverse effects on respiratory function and quality of life. Objectives: The objective of this study was to assess the effect of therapeutic bronchoscopic interventions on spirometry, dyspnea, quality of life, and survival in patients with CAO. Methods: We prospectively studied patients who underwent therapeutic rigid bronchoscopy for CAO. Spirometry, San Diego Shortness of Breath questionnaire (SOBQ), and SF-36 questionnaire responses were obtained before the procedure and at follow-up 6-8 weeks after the procedure. Results: Fifty-three patients (24 malignant and 29 nonmalignant CAO), who underwent successful rigid bronchoscopic intervention, were enrolled. Airway stent placement and various debulking techniques including mechanical debridement and heat therapy were used. After bronchoscopy, there was a significant increase in forced vital capacity (2.2 ± 0.91 l before, 2.7 ± 0.80 l after, p = 0.009) and forced expiratory volume at 1 s (1.4 ± 0.60 l before, 1.8 ± 0.67 l after, p = 0.002). The SOBQ score improved from 55.8 ± 30.1 before the procedure to 37.9 ± 27.25 after the procedure (p = 0.002). In the SF-36, there was an improvement in almost all domains, with statistically significant improvement seen in several domains. Benefits were seen independent of the etiology of CAO, site of intervention or stent placement. The patients with malignant CAO, in whom airway patency could not be achieved, had a poor survival. Conclusions: Alleviation of CAO with therapeutic rigid bronchoscopy results in improvement in spirometry, shortness of breath, quality of life, and survival.
Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for Moraxella catarrhalis
Authors: Abdillahi Suado M. , Bober Marta , Nordin Sara , Hallgren Oskar , Baumgarten Maria , Erjefält Jonas , Westergren-Thorsson Gunilla , Bjermer Leif , Riesbeck Kristian , Egesten Arne , Mörgelin Matthias
Published: April 2015

Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides potential adhesive targets. Collagen VI is a ubiquitous fibrillar component in the airway mucosa and has been attributed both adhesive and killing properties against Gram-positive bacteria. However, less is known regarding Gram-negative microorganisms. Therefore, in the present study, the interaction of M. catarrhalis with collagen VI was characterized. We found that collagen VI is upregulated in the airways of COPD patients and exposed upon epithelial desquamation. Ex vivo, we inoculated airway biopsies and fibroblasts from COPD patients with M. catarrhalis. The bacteria specifically adhered to collagen VI-containing matrix fibrils. In vitro, purified collagen VI microfibrils bound to bacterial surface structures. The primary adhesion target was mapped to the collagen VI α2-chain. Upon exposure to collagen VI, bacteria were killed by membrane destabilization in physiological conditions. These previously unknown properties of collagen VI provide novel insights into the extracellular matrix innate immunity by quickly entrapping and killing pathogen intruders.
Astaxanthin Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis
Authors: Liu Guoyong , Shi Yan , Peng Xiaofei , Liu Hong , Peng Youming , He Liyu
Published: April 2015

Background/Aim: Focal segmental glomerulosclerosis (FSGS) is a specific pattern of chronic renal injury with progressive glomerular scarring. The phenotypic alterations that contribute to FSGS include inflammatory response and oxidative stress. Astaxanthin (ATX) has a broad range of biological functions, particularly antioxidant and anti-inflammatory ones. This study was designed to evaluate the renoprotective effect of ATX treatment on Adriamycin-induced FSGS. Methods: In Balb/c mice, Adriamycin nephropathy was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were treated with ATX (50 mg/kg body weight) once daily by oral gavage, again starting on the day of Adriamycin injection and continued for 6 weeks. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. Results: Animals that underwent intermittent exposure to ATX treatment exhibited significant improvements in renal functional parameters as well as in glomerular and interstitial fibrosis compared to those undergoing saline treatment in FSGS mouse models. ATX treatment exerted anti-inflammatory and antioxidant effects by promoting Nrf2 expression and suppressing renal nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome activation. Conclusion: ATX might offer a ray of hope for ameliorating FSGS.
Gemcitabine Plus Vinorelbine as the Second-Line Treatment and Beyond in Elderly Patients with Platinum-Pretreated Advanced Non-Small Cell Lung Cancer
Authors: Go Se-Il , Lee Won Sup , Lee Gyeong-Won , Kang Jung Hun , Kang Myoung Hee , Song Haa-Na , Lee Anna , Lee Un Seok , Choi Hye Jung , Kim Hoon-Gu
Published: April 2015

Background: The efficacy and tolerance of a gemcitabine and vinorelbine (GV) combination as salvage therapy have not been reported in elderly patients with advanced non-small cell lung cancer (NSCLC). Methods: We reviewed elderly patients with advanced NSCLC who had disease progression after one or more chemotherapy regimens, at least one including platinum, and then who were treated with GV as the salvage therapy. Results: In total 40 patients were analyzed. GV was at least the third-line chemotherapy in 24 patients (60.0%). Only 2 patients (5.0%) experienced grade 3 febrile neutropenia. Nonhematologic toxicities were generally mild and there was no treatment-related mortality. Among 29 patients evaluable for treatment response, 10 (34.5%) and 9 (31.0%) achieved a partial response and stable disease, respectively. The median overall survival was 10.3 months and the median progression-free survival was 3.1 months. Conclusions: GV in combination is an effective and tolerable salvage regimen in elderly and heavily pretreated patients with advanced NSCLC.
Predictive Markers of Tubo-Ovarian Abscess in Pelvic Inflammatory Disease
Authors: Lee Suk Woo , Rhim Chae Chun , Kim Jang Heub , Lee Sung Jong , Yoo Sie Hyeon , Kim Shin Young , Hwang Young Bin , Shin So Young , Yoon Joo Hee
Published: April 2015

Background/Aims: The purpose of this study was to identify predictive markers for tubo-ovarian abscess (TOA) through a comparison of clinical and laboratory data in patients diagnosed with pelvic inflammatory disease (PID). Methods: We reviewed the medical charts of 499 females who were admitted to hospital with clinical, surgical, imaging-based diagnoses of PID between 2001 and 2011. The patients were divided into the following two groups: (1) PID with TOA and (2) PID without TOA. Results: The TOA and non-TOA groups were comprised of 69 and 430 females, respectively. Mean age, history of intrauterine device (IUD) insertion and inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein (CRP) and CA-125 levels, were higher in the TOA group than the non-TOA group. Independent factors that predicted TOA were older age, IUD insertion, increased CRP and CA-125, and chlamydia infection. CA-125 was found to have the highest predictive value for TOA. TOA size was associated with increased surgical therapy compared to patients with smaller abscesses. Conclusions: Increased age, IUD insertion, chlamydia infection, and increased CRP and CA-125 level were the independent factors predictive of TOA in acute PID. These predictive values will be expected to help decrease gynecological morbidity by early diagnosis and appropriate treatment of TOA.
Eleven Years of Data on the Jefferson Scale of Empathy-Medical Student Version (JSE-S): Proxy Norm Data and Tentative Cutoff Scores
Authors: Hojat Mohammadreza , Gonnella Joseph S.
Published: April 2015

Objective: This study was designed to provide typical descriptive statistics, score distributions and percentile ranks of the Jefferson Scale of Empathy-Medical Student version (JSE-S) of male and female medical school matriculants to serve as proxy norm data and tentative cutoff scores. Subjects and Methods: The participants were 2,637 students (1,336 women and 1,301 men) who matriculated at Sidney Kimmel (formerly Jefferson) Medical College between 2002 and 2012, and completed the JSE at the beginning of medical school. Information extracted from descriptive statistics, score distributions and percentile ranks for male and female matriculants were used to develop proxy norm data and tentative cutoff scores. Results: The score distributions of the JSE tended to be moderately skewed and platykurtic. Women obtained a significantly higher mean score (116.2 ± 9.7) than men (112.3 ± 10.8) on the JSE-S (t2,635 = 9.9, p < 0.01). It was suggested that percentile ranks can be used as proxy norm data. The tentative cutoff score to identify low scorers was ≤95 for men and ≤100 for women. Conclusions: Our findings provide norm data and cutoff scores for admission decisions under certain conditions and for identifying students in need of enhancing their empathy.
Characterization of Markers of the Progression of Human Parvovirus B19 Infection in Virus DNA-Positive Plasma Samples
Authors: Bonjoch Xavier , Obispo Francesc , Alemany Cristina , Pacha Ana , Rodríguez Esteban , Xairó Dolors
Published: April 2015

Background: Accurate characterization of the infection stage in parvovirus B19(B19V)-positive plasma donations would help establish the donation deferral period to contribute to a safe fractionation pool of plasma. Methods: Viral DNA load of 74 B19V DNA-positive plasma samples from whole blood donations was determined by titration using nucleic acid testing. Markers of cellular (neopterin) and humoral (B19V-specific IgM and IgG) immune response were determined by ELISA in 32 B19V DNA-positive samples and in 13 B19V DNA-negative samples. The infection progression profile was estimated according to B19V DNA load and the presence of immune response markers. Results: B19V DNA load in the 74 samples was 106-1013 IU/ml. The distribution of 14 out of 32 selected B19V DNA-positive samples plus 2 B19V DNA-negative samples with no immune response marker followed along an upward curve according to B19V DNA load. After the peak, the distribution of 18 immune marker-positive samples followed along a downward curve according to their B19V DNA load and was grouped as follows: neopterin (n = 4), neopterin+ IgM (n = 8), neopterin + IgM + IgG (n = 3), IgM + IgG (n = 2), IgM (n = 1). There were 11 B19V DNA-negative IgG-positive samples. Conclusion: This study of B19V-DNA load and levels of neopterin, IgM, and IgG allows for reliable characterization and distribution into the different stages of B19V infection.
Functional outcome of prolonged refractory status epilepticus
Authors: Lai Alexandre , Outin Hervé D , Jabot Julien , Mégarbane Bruno , Gaudry Stéphane , Coudroy Rémi , Louis Guillaume , Schneider Francis , Barbarot Nicolas , Roch Antoine , Lerolle Nicolas , Luis David , Fourrier François , Renault Anne , Argaud Laurent , Sharshar Tarek , Gibot Sébastien , Bollaert Pierre-Edouard
Published: April 2015

Introduction

To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors.

Methods

Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0–3 defining good and mRS 4–6 poor outcome.

Results

78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12–26) days. The median length of ICU stay was 28 (19–48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04).

Conclusion

Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.
Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis
Authors: Li Pengfei , Guo Youming , Bledsoe Grant , Yang Zhi-Rong , Fan Hongkuan , Chao Lee , Chao Julie
Published: April 2015

Introduction

Kallistatin levels in the circulation are reduced in patients with sepsis and liver disease. Transgenic mice expressing kallistatin are resistant to lipopolysaccharide (LPS)-induced mortality. Here, we investigated the effect of kallistatin on survival and organ damage in mouse models of established sepsis.

Methods

Mice were rendered septic by cecal ligation and puncture (CLP), or endotoxemic by LPS injection. Recombinant human kallistatin was administered intravenously six hours after CLP, or intraperitoneally four hours after LPS challenge. The effect of kallistatin treatment on organ damage was examined one day after sepsis initiation, and mouse survival was monitored for four to six days.

Results

Human kallistatin was detected in mouse serum of kallistatin-treated mice. Kallistatin significantly reduced CLP-induced renal injury as well as blood urea nitrogen, serum creatinine, interleukin-6 (IL-6), and high mobility group box-1 (HMGB1) levels. In the lung, kallistatin decreased malondialdehyde levels and HMGB1 and toll-like receptor-4 (TLR4) synthesis, but increased suppressor of cytokine signaling-3 (SOCS3) expression. Moreover, kallistatin attenuated liver injury, serum alanine transaminase (ALT) levels and hepatic tumor necrosis factor-α (TNF-α) synthesis. Furthermore, delayed kallistatin administration improved survival in CLP mice by 38%, and LPS-treated mice by 42%. In LPS-induced endotoxemic mice, kallistatin attenuated kidney damage in association with reduced serum creatinine, IL-6 and HMGB1 levels, and increased renal SOCS3 expression. Kallistatin also decreased liver injury in conjunction with diminished serum ALT levels and hepatic TNF-α and TLR4 expression. In cultured macrophages, kallistatin through its active site increased SOCS3 expression, but this effect was blocked by inhibitors of tyrosine kinase, protein kinase C and extracellular signal-regulated kinase (ERK), indicating that kallistatin stimulates a tyrosine-kinase-protein kinase C-ERK signaling pathway.

Conclusions

This is the first study to demonstrate that delayed human kallistatin administration is effective in attenuating multi-organ injury, inflammation and mortality in mouse models of polymicrobial infection and endotoxemia. Thus, kallistatin therapy may provide a promising approach for the treatment of sepsis in humans.
Mutation signatures implicate aristolochic acid in bladder cancer development
Authors: Poon Song Ling , Huang Mi Ni , Choo Yang , McPherson John R , Yu Willie , Heng Hong Lee , Gan Anna , Myint Swe Swe , Siew Ee Yan , Ler Lian Dee , Ng Lay Guat , Weng Wen-Hui , Chuang Cheng-Keng , Yuen John SP , Pang See-Tong , Tan Patrick , Teh Bin Tean , Rozen Steven G
Published: April 2015

Background

Aristolochic acid (AA) is a natural compound found in many plants of the Aristolochia genus, and these plants are widely used in traditional medicines for numerous conditions and for weight loss. Previous work has connected AA-mutagenesis to upper-tract urothelial cell carcinomas and hepatocellular carcinomas. We hypothesize that AA may also contribute to bladder cancer.

Methods

Here, we investigated the involvement of AA-mutagenesis in bladder cancer by sequencing bladder tumor genomes from two patients with known exposure to AA. After detecting strong mutational signatures of AA exposure in these tumors, we exome-sequenced and analyzed an additional 11 bladder tumors and analyzed publicly available somatic mutation data from a further 336 bladder tumors.

Results

The somatic mutations in the bladder tumors from the two patients with known AA exposure showed overwhelming AA signatures. We also detected evidence of AA exposure in 1 out of 11 bladder tumors from Singapore and in 3 out of 99 bladder tumors from China. In addition, 1 out of 194 bladder tumors from North America showed a pattern of mutations that might have resulted from exposure to an unknown mutagen with a heretofore undescribed pattern of A > T mutations. Besides the signature of AA exposure, the bladder tumors also showed the CpG > TpG and activated-APOBEC signatures, which have been previously reported in bladder cancer.

Conclusions

This study demonstrates the utility of inferring mutagenic exposures from somatic mutation spectra. Moreover, AA exposure in bladder cancer appears to be more pervasive in the East, where traditional herbal medicine is more widely used. More broadly, our results suggest that AA exposure is more extensive than previously thought both in terms of populations at risk and in terms of types of cancers involved. This appears to be an important public health issue that should be addressed by further investigation and by primary prevention through regulation and education. In addition to opportunities for primary prevention, knowledge of AA exposure would provide opportunities for secondary prevention in the form of intensified screening of patients with known or suspected AA exposure.
Comparison and evaluation of lupus nephritis response criteria in lupus activity indices and clinical trials
Authors: Corapi Kristin M , Dooley Mary Anne , Pendergraft William F
Published: April 2015

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations. Although the approval of new therapies includes only one agent in 50 years, a number of promising new drugs are in development. Lupus nephritis is a dreaded complication of SLE as it is associated with significant morbidity and mortality. Advancing the treatment of lupus nephritis requires well-designed clinical trials and this can be challenging in SLE. The major obstacles involve identifying the correct population of patients to enroll and ensuring that a clinically appropriate and patient-centered endpoint is being measured. In this review, we will first discuss the clinical utility of endpoints chosen to represent lupus nephritis in global disease activity scales. Second, we will review completed and active trials focused on lupus nephritis and discuss the endpoints chosen. There are many important lessons to be learned from existing assessment tools and clinical trials. Reviewing these points will help ensure that future efforts will yield meaningful disease activity measures and well-designed clinical trials to advance our understanding of lupus management.
Validated predictive computational methods for surface charge in heterogeneous functional materials: HeteroFoaM™
Authors: Reifsnider Kenneth L , Cacuci Dan G , Baker Jeffrey , Adkins Jon Michael , Rabbi Fazle
Published: April 2015

Background

Essentially all heterogeneous materials are dielectric, i.e., they are imperfect conductors that generally display internal charge displacements that create dissipation and local charge accumulation at interfaces. Over the last few years, the authors have focused on the development of an understanding of such behaviour in heterogeneous functional materials for energy conversion and storage, called HeteroFoaM (www.HeteroFoaM.com). Using paradigm problems, this work will indicate major directions for developing generally applicable methods for the multiphysics, multi-scale design of heterogeneous functional materials.

Methods

The present paper outlines the foundation for developing validated predictive computational methods that can be used in the design of multi-phase heterogeneous functional materials, or HeteroFoaM, as a genre of materials. Such methods will be capable of designing not only the constituent materials and their interactions, but also the morphology of the shape, size, surfaces and interfaces that define the heterogeneity and the resulting functional response of the material system.

Results

Relationships to applications which drive this development are identified. A paradigm problem based on dielectric response is formulated and discussed in context.

Conclusions

We report an approach that defines a methodology for designing not only the constituent material properties and their interactions in a heterogeneous dielectric material system, but also the morphology of the shape, size, surface, and interfaces that defines the heterogeneity and the resulting functional response of that system.
Forward and backward amplitude and phase estimation method for dispersion analysis of borehole sonic measurements
Authors: Li Wei , Tao Guo , Matuszyk Paweł J. , Torres-Verdín Carlos
Published: April 2015

We have developed a nonparametric matched filter-bank spectrum estimator, referred to as the forward and backward (FB) amplitude and phase estimation (FBAPES) method, to perform dispersion analysis of borehole array sonic measurements. Different from conventional dispersion analysis methods, the amplitude and phase estimation method estimates the dispersive properties of wave modes by simulating the statistical character of interferences from noise and other modes taking place at the same frequency, designing an adaptive filter to suppress these interferences, and fitting the filter output to a spatial sinusoid with a designated slowness. Such an adaptive filter with low side-lobe response gives rise to a high-resolution fitness function, with clear and narrow ridges, which significantly facilitates identification of different modes. At each frequency, for a data set with a moderate noise level, slowness of all modes hidden in the recorded waveforms can be identified without prior knowledge of the exact number of wave modes. We apply an FB method to improve the robustness of the estimation. We used synthetic and field examples to verify the advantages of the method over the weighted spectral semblance and extended matrix pencil methods. Resolution and noise analyses confirmed the high stability and resolution performance of the FBAPES method.
Beneficial Effect of Pentoxifylline on Thyroid Associated Ophthalmopathy (TAO)*: a pilot study
Authors: Balazs Cs. , Kiss E. , Vamos A. , Molnar I. , Farid N.R.
Published: April 2015

We have previously found that pentoxifylline (Ptx) inhibited cytokine induced HLA-DR expression and glycosaminoglycan (GAG) synthesis by retroorbital fibroblasts. We have now tested the clinical efficacy of Ptx in treating TAO. Ten patients with moderately severe ophthalmopathy were selected for study. All patients were euthyroid before and during the 12 weeks of the Ptx therapy. Serum GAG, TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies were determined sequentially. At the end of 12 weeks eight of the ten patients showed improvement in soft tissue but not in proptosis or extraocular muscle involvement. At baseline the levels of GAG (5.2±0.92 mg/dl v.s. 0.7±0.14 mg/dl, p<0.001) and TNF-alpha (33.6±6.6 pg/ml v.s. 5.4±1.3 pg/ml, p<0.001) were increased in patients compared to controls. They gradually decreased in the eight patients who responded to Ptx: after 4, 8 and 12 weeks of therapy serum GAG was 3.4±0.42 mg/dl, 2.5±0.77 mg/dl (p<0.01) and 1.1±0.2 mg/dl (p<0.001), respectively and serum TNF-alpha was 20.9±4.8 pg/ml, 14.9±2.2 pg/ml (p<0.05) and9.7±1.8 pg/ml (p<0.01), respectively. Serum GAG and TNF alpha did not fall in the two patients who did not respond. The titre of anti-eye muscle antibodies but not anti-thyroid antibodies were lower at 12 weeks. Ptx has a beneficial effect on inflammatory symptoms of TAO and associated laboratory parameters in the majority of patients.
Synthesis of 2,3-Benzodiazepines and 2,3-Benzodiazepin-4-ones from Arynes and β-Diketones
Authors: Okuma Kentaro , Tanabe Yukiko , Nagahora Noriyoshi , Shioji Kosei
Published: April 2015

2,3-Benzodiazepines were synthesized by two-step or one-pot reactions from aryne precursors. Reaction of 2-(trimethylsilyl)aryl triflates with β-diketones in the presence of CsF gave ortho-substituted benzophenones. Treatment of benzophenones with hydrazine hydrate resulted in the formation of 2,3-benzodiazepines in moderate yields. Tofisopam, a well known anxiolytic, could be synthesized via C–C bond insertion of 3,4-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in one-pot operation. 2,3-Benzodiazepin-4-ones were also synthesized by the reaction of β-keto esters with triflates in the presence of CsF, followed by the addition of hydrazine hydrate. Substituted isoquinolines were synthesized by the reaction of ortho-substituted benzophenones with ammonium hydroxide.
An Information Stock Model of Customer Behavior in Multichannel Customer Support Services
Authors: Jerath Kinshuk , Kumar Anuj , Netessine Serguei
Published: April 2015

We develop a model to understand and predict customers’ observed multichannel behavior in a customer support setting. Using individual-level data from a U.S.-based health insurance firm, we model a customer’s query frequency and choice of using the telephone or web channel for resolving queries as a stochastic function of her latent “information stock.” The information stock is a function of the customer’s “information needs” (which arise when customers file health insurance claims) and “information gains” (which customers obtain when they resolve their queries through the telephone and web support channels), and other factors such as seasonal effects (for instance, queries that arise at the time of annual contract renewal). We find that average information gain from a telephone call is twice as much as that from visiting the web portal; customers prefer the telephone channel for health event-related information but prefer the web portal for structured seasonal information; and customers are polarized in their propensities of using the web channel and can be broadly classified into “web avoiders” and “web seekers.” Our model provides superior in-sample and out-of-sample fit than multiple benchmark models for aggregate and individual-level customer activity and has several managerial uses, such as capacity planning.
Dynamic movement lycra orthosis in multiple sclerosis
Authors: Betts Liz
Published: April 2015

Conventional orthoses and dynamic lycra® orthoses are now being used in the management of symptoms commonly seen in multiple sclerosis (MS). In this article, the role of conventional orthoses and functional electrical stimulation for the lower limbs, affecting the gait cycle in both stance and swing phase, are described and categorised. Upper limb orthoses used for support of the shoulder and positioning of the wrist and hand and their effects on reducing pain and preventing contracture are discussed. Dynamic lycra orthoses can be used to manage abnormal tone and encourage function for people with MS. The compression gives strong sensory stimulation and the lycra panelling influences the positioning of the body to put it at a bio-mechanical advantage for movement. The effectiveness of this approach will be discussed in the context of the current literature on this topic.
Comparison of oesophageal, rectal and tympanic membrane temperature in anaesthetised client-owned cats
Authors: Watson FCE , Brodbelt DC , Gregory SP
Published: April 2015

Objectives:

To determine the agreement between a veterinary-specific tympanic membrane thermometer and measurement of core oesophageal and rectal temperature in client-owned anaesthetised cats.

Methods:

A prospective study was performed using 20 cats that were scheduled to undergo general anaesthesia. For each cat, five consecutive temperature recordings were taken from an oesophageal temperature probe (OT), rectal thermometer (RT) and a veterinary-specific tympanic membrane thermometer (TT) prior to surgery. The temperatures were compared using Bland-Altman analysis.

Results:

Mean differences for the TT compared with OT and RT were -0.86°C (SD = 0.62°C, 95% CI [-2.39°C, 0.67°C]) and -0.93°C (SD = 0.57°C, 95% CI [-2.27, 0.44]) respectively; both greater than the accepted maximal clinical tolerance of 0.20°C. The mean difference for the RT compared with the OT was 0.06°C (SD = 0.28°C, 95% CI [-0.56, 0.67]).

Clinical significance:

The TT does not accurately represent core body temperature in cats under general anaesthesia and should not be used interchangeably with oesophageal thermometers. Rectal temperatures can be used to reliably approximate core temperature in anaesthetised cats.
Who or What to Believe: Trust and the Differential Persuasiveness of Human and Anthropomorphized Messengers
Authors: Touré-Tillery Maferima , McGill Ann L.
Published: April 2015

Participants in three studies read advertisements in which messages were delivered either by people or by anthropomorphized agents—specifically, “talking” products. The results indicate that people low in interpersonal trust are more persuaded by anthropomorphized messengers than by human spokespeople because low trusters are more attentive to the nature of the messenger and believe that humans, more than partial humans (i.e., anthropomorphized agents), lack goodwill. People high in interpersonal trust are less attentive about who is trying to persuade them and so respond similarly to human and anthropomorphized messengers. However, when prompted to be attentive, they are more persuaded by human spokespeople than by anthropomorphized messengers due to their belief that humans, more than partial humans, act with goodwill. Under conditions in which attentiveness is low for all consumers, high and low trusters alike are unaffected by the nature of persuasion agents. The authors discuss the implications of the findings for advertisers considering the use of anthropomorphized “spokespeople.”
Biochemical and chemical indices of soil transformations on goose farms in years 1996–2011 / Biochemiczne i chemiczne wskaźniki przeobrażeń gleb na terenie ferm gęsi w latach 1998–2011
Authors: Bielińska Elżbieta Jolanta , Mocek-Płóciniak Agnieszka
Published: April 2015

The paper presents characterisation of the eco-chemical condition and potential threats to soils of goose farms on the basis of recent monitoring of a 15-year measuring cycle. It was demonstrated that the observed soil enzymatic inactivation progressing with years of investigations on the examined farms was significantly associated with a very high content of mineral nitrogen and available forms of phosphorus. A distinct tendency towards increased content of heavy metals in soils derived from these farms as well as in their direct neighbourhood observed with the passage of time poses a serious hazard to the environment