bluuebunny/crossref_metadata_2025 huggingface dataset:
P31 No interaction between doxapram and caffeine for the treatment of preterm neonates with apnea
Authors: Engbers A , Dia N , Völler S , Knibbe CAJ , Reiss IKM , Koch BCP , Flint RB , Simons SHP
Published: May 2019

Background

In preterm neonates with apneas, co-administration with doxapram is often initiated in case of inadequate response to caffeine alone. While doxapram is exclusively registered for adults, there is limited information on its use in preterm infants. To examine whether the observed effects of doxapram are actually due to doxapram itself, and not a pharmacokinetic interaction between both respiratory stimulants, we studied the pharmacokinetics (PK) of caffeine in a population of preterm neonates receiving both caffeine and doxapram.

Methods

Caffeine concentrations from patients in the DINO study (NCT02421068) who received both caffeine and doxapram were analyzed using NONMEM V7.3. A PK model of caffeine in preterm neonates was used as a basis to estimate the PK parameters of caffeine when co-administered with doxapram with F fixed to 1 and ka fixed to 1.48 h-1.1 The results of the current study were compared to those of the reference population published by Charles et al.1

Results

In 15 preterm infants 58 samples were collected in which caffeine plasma levels were determined. Median gestational age (GA) was 26.3 (range 24–28) weeks, postnatal age (PNA) was 25 (0–63) days and current weight was 1100 (600–2140) grams. Caffeine CL and Vd for an individual with a PNA of 12 days were estimated 0.2 L/h/70kg (RSE 28%) and 68.2 L/70kg (RSE 73%), respectively. Maturation of CL was best described by a power function with an exponent of 0.404 (RSE 89%). These results seem in good agreement with the reference population of preterm neonates receiving caffeine without doxapram with values of 0.167 L/kg/70 kg, 58.6 L/70kg and 0.358.1

Conclusion

In this pharmacokinetic study in preterm neonates receiving both caffeine and doxapram, we found similar values for CL, Vd and maturation of CL with PNA compared to literature values obtained in preterm neonates receiving caffeine alone.

References

BG C. et al. Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther. Drug Monit 2008;30:709–716.

Disclosure(s)

Nothing to disclose
P35 Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin in the paediatric population – a systematic literature investigation
Authors: Feickert M , Burckhardt BB
Published: May 2019

Background

In cell line experiments, the selective NK-1-receptor antagonist Aprepitant was able to inhibit the cardiotoxic adverse effects of Doxorubicin,1 a common cytostatic used in paediatric cancer therapies. Cytostatic therapy is one of the principal reasons for toxic cardiomyopathy in children, resulting in dilated cardiomyopathy and consequently leading to heart failure. However, Aprepitant is currently licenced for adults and children and is indicated amongst others in the antiemetic supportive therapy of Doxorubicin regimes. To address the hypothesis of any indication of Aprepitant in preventing cardiotoxic adverse effects of Doxorubicin, systematic literature research is needed.

Methods

Systematic literature research was examined using PubMed in January 2019. Selected inclusion criteria were: ‘Substance P’ or ‘Aprepitant’ and ‘Doxorubicin’/’cardiac inflammation’/’cardiomyopathy’ or ‘Aprepitant’ and ‘paediatrics’/’neonates’/’children’. The use of Aprepitant in adults and children as an antiemetic agent and the involvement of Substance P in (neurogenic) inflammation, cardiac infarction or diabetes led to the exclusion of publications.

Results

The PubMed search resulted in 220 identified publications whereby 33 were relevant concerning the potential use of Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin. It emphasises the potential use of Aprepitant in the prevention of toxic cardiomyopathy by antagonizing the inflammatory effects of the endogenous NK-1-agonist Substance P regarding cell and animal models.1 2 Based on these models, Substance P is associated with adverse cardiac remodelling and cardiac inflammation. However, in children, Aprepitant was only used as an antiemetic agent and no off-label indication was described.

Conclusion

Since toxic cardiomyopathy is a severe adverse effect in the Doxorubicin therapy in children, the evaluation of the role of Substance P is a promising and worthy approach to condense the knowledge about a potential use of Aprepitant in preventing paediatric toxic cardiomyopathy.

References

Robinson P, Kasembeli M, Bharadwaj U, et al. Substance P receptor signaling mediates doxorubicin-induced cardiomyocyte apoptosis and triple-negative breast cancer chemoresistance. Biomed Res Int2016; 2016. doi:10.1155/2016/1959270

Levick SP, Soto-Pantoja DR, Bi J, et al. Doxorubicin-induced myocardial fibrosis involves the neurokinin-1 receptor and direct effects on cardiac fibroblasts. Heart Lung Circ. Published Online First: September 2018. doi:10.1016/j.hlc.2018.08.003

Disclosure(s)

Martin Feickert and Bjoern B. Burckhardt declare that there is no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
When biology supports clinical diagnosis: review of techniques to diagnose ocular toxoplasmosis
Authors: Greigert Valentin , Di Foggia Elsa , Filisetti Denis , Villard Odile , Pfaff Alexander W , Sauer Arnaud , Candolfi Ermanno
Published: May 2019

Toxoplasmosis is a common infection whose worldwide prevalence is estimated at 30%, with large disparities across the world. Among infected subjects, the prevalence of ocular toxoplasmosis (OT) is, however, limited to about 2% in Europe and 17% in South America. In France, it is estimated that about 1 000 000 patients present either active OT or subsequent chorioretinal scars. Toxoplasmagondii is the first cause of posterior uveitis worldwide, responsible for retinochoroiditis, at times associated with anterior uveitis. To date, there is no consensus yet on how to diagnose OT, which is often based only on clinical presentation. Nevertheless, OT-associated symptoms are often atypical and misleading. Over the last 20 years, tremendous progress has been made in biological tools, enabling parasitologists to confirm the diagnosis in most suspected cases of OT. Using anterior chamber puncture, a safe and fast procedure, ophthalmologists sample aqueous humour for analysis using multiple techniques in order to reach high specificity and sensitivity in OT diagnosis. In this article, we present the different techniques available for the biological diagnosis of OT, along with their characteristics, and propose a diagnostic algorithm designed to select the best of these techniques if clinical examination is not sufficient to ascertain the diagnosis.
Modelling hospital operations: insight from using data from paper registries in the obstetrics ward at a hospital in Addis Ababa, Ethiopia
Authors: Bigelow Benjamin , Desalegn Dawit N , Salomon Joshua A , Verguet Stéphane
Published: May 2019

In the Ethiopian health system, operations management techniques have been underutilised. Although previous research has outlined limitations of paper-based patient records, few studies have examined their potential utility for improving management of hospital operations. In this paper, we used data collected from paper registries in an Ethiopian obstetrics ward at Addis Ababa’s Tikur Anbessa Specialized Hospital, Ethiopia’s largest university hospital, to model the ward’s operations. First, we attempted to identify predictors of lengthy stays and readmissions among women giving birth: few predictors were deemed significant. Second, time series methods for demand forecasting were applied to the data and evaluated with several error metrics, and these forecasts were improvements over baseline methods. We conclude with recommendations on how the obstetrics ward could incorporate our modelling approaches into their daily operations.
Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years
Authors: Vuik Fanny ER , Nieuwenburg Stella AV , Bardou Marc , Lansdorp-Vogelaar Iris , Dinis-Ribeiro Mário , Bento Maria J , Zadnik Vesna , Pellisé María , Esteban Laura , Kaminski Michal F , Suchanek Stepan , Ngo Ondřej , Májek Ondřej , Leja Marcis , Kuipers Ernst J , Spaander Manon CW
Published: May 2019

Objective

The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years.

Design

Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change.

Results

We retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively.

Conclusion

CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.
Incidences, temporal trends and risks of hospitalisation for gastrointestinal bleeding in new or chronic low-dose aspirin users after treatment forHelicobacter pylori: a territory-wide cohort study
Authors: Guo Chuan-Guo , Cheung Ka Shing , Zhang Feifei , Chan Esther W , Chen Lijia , Wong Ian CK , Leung Wai K
Published: May 2019

Objective

The risk of GI bleeding (GIB) in aspirin users afterHelicobacter pylori(HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy.

Design

Based on a territory-wide health database, we identified all patients who had received the first course of clarithromycin-based triple therapy between 2003 and 2012. Patients were divided into three cohorts according to aspirin use: new users (commenced after HP eradication), chronic users (commenced before and resumed after HP eradication) and non-users. The primary outcome was to determine the risk of hospitalisation for GIB.

Results

We included 6985 new aspirin users, 5545 chronic users and 48 908 non-users. The age-adjusted and sex-adjusted incidence of hospitalisation for all GIB in new, chronic and non-users was 10.4, 7.2 and 4.6 per 1000 person-years, respectively. Upper and lower GIB accounted for 34.7% and 45.3% of all bleeding, respectively. Compared with chronic users, new users had a higher risk of GIB (HR with propensity score matching: 1.89; 95% CI 1.29 to 2.70). Landmark analysis showed that the increased risk in new aspirin users was only observed in the first 6 months for all GIB (HR 2.10, 95% CI 1.41 to 3.13) and upper GIB (HR 2.52, 95% CI 1.38 to 4.60), but not for lower GIB.

Conclusion

New aspirin users had a higher risk of GIB than chronic aspirin users, particularly during the initial 6 months. Lower GIB is more frequent than upper GIB in aspirin users who had HP eradicated.
Response to BotulinumtoxinA in a migraine cohort with multiple comorbidities and widespread pain
Authors: Barad Meredith , Sturgeon John Andrew , Fish Shannon , Dexter Franklin , Mackey Sean , Flood Pamela Dru
Published: May 2019

Background

The phase III research evaluating migraine prophylaxis therapy (PREEMPT) protocol was developed in low-risk migraine patients. We studied longitudinal response to treatment in a sequential retrospective observational cohort to evaluate predictors of effectiveness in patients with multiple overlapping pain syndromes treated in a quaternary pain management clinic.

Methods

We evaluated indicators of individual response in 402 consecutive chronic migraine patients who provided demographic information and used the Collaborative Health Outcomes Information Registry.

Results

The patients were middle aged 47 (38–56) median (IQR) years old and 83% women. They reported multiple complex pain problems with 11 (6–18) regions represented on a pain body map. Evaluated with National Institutes of Health Patient-Reported Outcomes Measurement Information System measures, they reported higher scores for sleep impairment and disturbance, anxiety, depression, fatigue, pain behavior, pain interference and worse function and satisfaction with social roles compared with the general US population; p<0.001 for all domains. Within 120 days of treatment, 62% of patients reported reduced headache frequency. The best multivariable model developed for prediction of reduced headache frequency in response to treatment included lower treatment number, lower pain interference score, and less depression (p=0.001, 0.002, and 0.009). Depression may have been an obstacle to successful treatment; there was no association between depression score and number of treatments (p=0.54).

Conclusions

Our findings point to the importance of identifying and addressing pain interference and depression early in chronic migraine management and, more broadly, highlights the importance of multidisciplinary evaluation and treatment in chronic migraine.
Acceptability and feasibility of using digital vending machines to deliver HIV self-tests to men who have sex with men
Authors: Vera Jaime H , Soni Suneeta , Pollard Alex , Llewellyn Carrie , Peralta Carlos , Rodriguez Liliana , Dean Gillian
Published: May 2019

Objective

Technology-based approaches to distribute HIV self-tests (HIVST) have the potential to increase access to HIV testing in key populations. We evaluate the acceptability and feasibility of using vending machines (VMs) in a community setting to distribute HIVST to men who have sex with men at high-risk of HIV.

Methods

First, a predevelopment survey of targeted potential users explored attitudes towards HIVST and the use of a VM to deliver HIVST. Second, participatory design workshops between designers and community volunteers informed the production of a bespoke VMs dispensing free BioSureHIVST. Uptake of HIVST and user experiences were evaluated using information supplied directly from the machines interface (number of tests dispensed, user demographics), an online questionnaire and semistructured interviews.

Results

The predevelopment survey found that 32% of 232 sauna users had never tested for HIV, despite high-risk behaviours. A total of 265 testing kits were dispensed: mean age 31 range (18–70); 4%(n = 7) had never tested for HIV before and 11% (n = 22) had tested within the last 1–5 years. Uptake of tests was significantly higher via the VMs compared with outreach testing by community workers in the same venue during a comparable period (34 vs 6 tests per month). Qualitative interviews and online questionnaires demonstrated high acceptability for this intervention, which was considered accessible and appropriately targeted.

Conclusions

VMs to distribute HIVST was feasible and acceptable. This intervention could be used in different settings to improve access to HIV testing for key populations
Possible drug‐induced follicular mucinosis in a dog
Authors: Lima Tatiana de Brito , Ordeix Laura , Fondevila Dolors
Published: May 2019

A nine‐year‐old, entire male basset hound presented with one‐year history of pruritus and patchy to diffuse alopecia accompanied by erythema, starting a few days after applying an implant of deslorelin for treatment of benign prostatic hyperplasia. Dermatopathological examination was diagnostic for follicular mucinosis, accompanied by a characteristic lymphocytic mural folliculitis at the level of the isthmus. Partial improvement with anti‐inflammatory doses of prednisone was observed. Thereafter, oral ciclosporin was administered on a daily regimen until complete remission was achieved, after which it was gradually tapered until withdrawal. No other implants were applied thereafter, and two years later the patient remains free of clinical signs.
Synchronous bilateral testicular neoplasms in a black‐capped capuchin (Sapajus apella)
Authors: Fraess Garrett , Dickinson Ryan , Kragness Brandy , Sadar Miranda
Published: May 2019

A 31‐year‐old, 5.01 kg, intact male black‐capped capuchin (Sapajus apella) was presented for examination after zookeepers noted an enlarged right testicle. Fine‐needle aspiration with cytological evaluation identified a seminoma of the right testis. Castration was elected for this non‐breeding male, and both testicles were submitted for histopathology. Histopathology confirmed the presence of a seminoma in the right testicle and, incidentally, a mass in the left testis consistent with an interstitial cell tumour was also diagnosed. This report describes the first case of seminoma or interstitial cell neoplasia in a black‐capped capuchin, as well as the first case of a non‐human primate with synchronous, bilateral testicular neoplasms.
Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder
Authors: Zastrozhin M.S. , Skryabin V.Y. , Smirnov V.V. , Grishina E.A. , Ryzhikova K.A. , Chumakov E.M. , Bryun E.A. , Sychev D.A.
Published: May 2019

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.
Network analysis of coal mine hazards based on text mining and link prediction
Authors: Wang Ze , Li Huajiao , Tang Renwu
Published: May 2019

Hazards are a potential source of harm and damage hiding in shadow zones. Without control, they may accumulate and interact with other types of hazards. In the harsh and complicated circumstance, especially, the deep underground space of coal mines, complex and nonlinear interactions among hazards multiply the probabilities that a hazard turns into accidents, more seriously, its effect may trigger more correlated hazards to worsen the accidents and bring huge loss of lives and assets. Therefore, identifying the correlations among hazards and understanding the complexity of interactions among coal mine hazards are significant for ensuring the safety of coal production. From this standpoint, we propose a hybrid method combing text mining and complex network method. First, we abstract the dangerous hazards from a large amount of text data. Then, we establish the coal mine hazard network (CMHN) to capture correlations among hazards. Finally, we analyze and predict the correlations among hazards based on CMHN. Through which, we find the fault-prone hazard and the recurrent hazards, more importantly, we figure out the nonlinear correlations among hazards and reveal the connection preference of hazards. Furthermore, we forecast the unknown correlations among hazards to take precautions of them. This study could be helpful for making prevention strategies for safety management in the coal mine and other highly dangerous industries.
University ranking based on faculty hiring network with minimum weighted violation rankings
Authors: Lang Liqian , Wang Yan , Chen Qinghua , Zheng Tao
Published: May 2019

University ranking arouses widespread interest among the society and the scientific community. It can cause resources to be allocated to the entity which has a higher ranking to make tremendous uneven distribution of resources such as funds, faculty, students and so on. Every year various controversial university rankings are issued by different institutions or individuals. However, they have to deal with a huge amount of data and cumbersome computing in their research. Furthermore, during the process of calculation, some key indicators are unreliable, subjective, and difficult to obtain or compute so that their results are easily questioned. An accurate and objective university ranking is important and necessary, but it still remains to be solved. In 2015, Clauset et al. creatively studied university rankings based on faculty hiring network with graduation-employment flow data. They used the minimum violation ranking (MVR) method to get a university ranking which has a high correlation with U.S. News & World Report (USN) and National Research Council (NRC) Ranking, implying a strong consistency between them. This method costs less and is also objective. Inspired by this thought, this paper proposed a new ranking algorithm with minimum weighted violation rankings derived through maximum likelihood estimation. This assumption is more reasonable, and the results are commendably consistent with the rankings of renowned agencies. This more general method is more flexible than non-weighted calculation. More importantly, this work revealed the essential mechanism of MVR by deriving maximum likelihood.
MHD nanofluid heat transfer between a stretching sheet and a porous surface using neural network approach
Authors: Geng Yuancheng , Hassanvand A. , Monfared Mostafa , Moradi Rasoul
Published: May 2019

Magnetohydrodynamic flow of nanofluids and heat transfer between two horizontal plates in a rotating system have been examined numerically. In order to do this, the group method of data handling (GMDH)-type neural networks is used to calculate Nusselt number formulation. Results indicate that GMDH-type NN in comparison with fourth-order Runge–Kutta integration scheme provides an effective means of efficiently recognizing the patterns in data and accurately predicting a performance. Single-phase model is used in this study. Similar solution is used in order to obtain ordinary differential equation. The effects of nanoparticle volume fraction, magnetic parameter, wall injection/suction parameter and Reynolds number on Nusselt number are studied by sensitivity analyses. The results show that Nusselt number is an increasing function of Reynolds number and volume fraction of nanoparticles but it is a decreasing function of magnetic parameter. Also, it can be found that wall injection/suction parameter has no significant effect on rate of heat transfer.
Optimization design of a novel zigzag lattice phononic crystal with holes
Authors: Zhang Z. , Ji G. M. , Han X. K.
Published: May 2019

A new zigzag lattice phononic crystal with holes is designed. Nondominated sorting genetic algorithm-II (NSGA-II) is used for the optimization of the newly designed phononic crystal (PC). Results indicate that geometrical parameters are key factors as well as density and elastic modulus for the determination of the bandgaps (BGs). The width of the BG of the optimized PC with holes can be increased three times higher than the initial design without holes.
Effect of hopping rates coupled with on-ramp on the phase diagrams of totally asymmetric simple exclusion process
Authors: Xiao Song , Chen Xiaoyu , Shi Jianhui , Liu Yanna
Published: May 2019

In this paper, the effect of different hopping rates coupled with on-ramp on the phase diagrams has been investigated by totally asymmetric simple exclusion process (TASEP). The topology of phase diagrams on different hopping rates and on-ramp has been obtained. Additionally, the corresponding phase diagrams and the existing condition are given by approximate mean field theory, and the theoretical results agree well with Monte Carlo simulations.
Improvement of flexural strength and compressive strength by heat treatment of PLA filament for 3D-printing
Authors: Hong Jeong-Hyo , Yu Tianyu , Chen Zixuan , Park Soo-Jeong , Kim Yun-Hae
Published: May 2019

Poly-lactic Acid (PLA) is an environmentally friendly material with better stability in heat shrinkage than Acrylonitrile Butadiene Styrene (ABS), such as warping in 3D printing. This study focused on the enhancement of the mechanical properties of PLA filament for 3D printers through different heat treatment temperature and heat exposure time of PLA samples. The results showed that the highest flexural strength was recorded in the PLA sample that went through heat treatment at [Formula: see text] and heat exposure time of 300 s. And it tended to decrease with temperature and time after this point. But it has higher flexural strength than neat PLA. The compressive strength showed the highest compressive strength through heat treatment at [Formula: see text] for 600 s. Because compressive strength has no threshold limit temperature in experimental temperature, compressive strength showed a tendency to increase with increasing heat exposure time and high temperature at same condition. This result showed that the heat treatment process affects the flexural strength and compressive strength and can be improved upon using appropriate heat treatment conditions.
Surface functionalization of PANI and PANI/ZnO hybrid nanofibers with metallic catalysts for ammonia sensing at room temperature
Authors: Zoshki Azam , Rahmani Mohammad Bagher , Masdarolomoor Fatemeh , Pilehrood Saeid Hessami
Published: May 2019

Four different sensor devices were fabricated using the deposition of gold and nickel on top of polyaniline and polyaniline/zinc oxide composite thin films on glass substrates. Prepared samples were characterized using field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy and UV-Visible spectroscopy. FESEM images confirmed the formation of interwoven nanofibers for all samples with the mean diameter of about 90 nm for PANI. The responses of the prepared samples toward various concentrations of ammonia gas were investigated by conductometric measurements at room temperature. The responses of the fabricated sensors toward 100 ppm of NH3 were obtained to be 112%, 3%, 177% and 148% for PANI/Au, PANI/Ni, PANI/ZnO/Au and PANI/ZnO/Ni samples, respectively. Results show both Ni and Au thin films as a metallic catalyst on top of PANI/ZnO nanocomposite can greatly improve the sensing characteristics toward NH3 at room temperature. However, PANI/ZnO/Au has the highest response with the lowest response time (4 s). The mechanism for the sensitivity enhancement of the fabricated devices was discussed.
NUMERICAL INVESTIGATION OF THE EFFECTS OF BED SHAPE ON THE END-TO-SIDE CABG HEMODYNAMICS
Authors: RAMEZANPOUR MEHDI , MAEREFAT MEHDI , RAMEZANPOUR NAHID , MOKHTARI-DIZAJI MANIJHE , ROSHANALI FARIDEH , NEZAMI FARHAD RIKHTEGAR
Published: May 2019

Disrupted flow initiates and aggravates intimal thickening in the end-to-side (ETS) coronary artery bypass grafting (CABG), which may lead to failure. To enhance the post-intervention hemodynamics, the geometry is either optimized or totally reconfigured. Majority of configurations proposed by researchers have not suited CABG surgery, for they entailed rigorous manipulation on conventional grafts in situ, which was neither swift nor straightforward. The aim of the present study is, thus, to introduce a slight, yet effective, modification to a conventional ETS CABG configuration, and numerically investigate its effects on updated hemodynamic and structural environment, anticipating the longevity of proposed configuration and CABG success. This fairly simple modification may easily be made positioning a pre-designed anastomotic device between the bed of host artery in the conventional ETS CABG and its surrounding tissues. Conducting comprehensive numerical simulations, performance of the proposed configuration was assessed using idealized and patient-specific geometries of the conventional ETS CABG. Blood flow was simulated in a conventional and an updated CABG configuration considering 2-way fluid–structure interaction. Results revealed that, although the proposed configuration may induce higher structural stresses in vessels walls, it may improve important hemodynamic metrics such as wall shear stress gradient, oscillatory shear index, and relative residence time on host artery bed reducing disruption of flow. This study may also set the stage for design engineers and regulatory officials to evolve ETS CABG toward more hemodynamics-friendly approaches. Further in vitro, preclinical, and clinical experiments are, yet, entailed to accomplish ideal designs of procedural guidelines/grafts.
Analysis and optimization based on a sex pheromone and pesticide pest model with gestation delay
Authors: Xiang Shu , Pei Yongzhen , Liang Xiyin
Published: May 2019

Sex pheromone, aiming at mating disruption (MD), being species specific and leaving no toxic residues in the produce grown, offers an attractive alternative to conventional pesticides. In this paper, by incorporating the gestation delay and sex pheromone, we explore the impact of MD control on the dynamic behaviors of pest system. Firstly, the boundness, stability and bifurcation of system are deliberated. Secondly, an optimal control problem based on sex pheromone and pesticide is transformed into an equivalent optimal parameter selection problem by introducing the constrain violation function. Additionally, the gradients of the cost function with respect to the dose of sex pheromone and the killing rate are given. Furthermore, simulations are executed to validate the validity of our method. Meanwhile, our results indicate that gestation delay increases the extinction risk of the population and liberating sex pheromone destroys the stability of equilibrium states.
Social Network De-anonymization
Authors: Qian Jianwei , Li Xiang-Yang , Jung Taeho , Fan Yang , Wang Yu , Tang Shaojie
Published: May 2019

Previous works on social network de-anonymization focus on designing accurate and efficient de-anonymization methods. We attempt to investigate the intrinsic relationship between the attacker’s knowledge and the expected de-anonymization gain. A common intuition is that more knowledge results in more successful de-anonymization. However, our analysis shows this is not necessarily true if the attacker uses the full background knowledge for de-anonymization. Our findings leave intriguing implications for the attacker to make better use of the background knowledge for de-anonymization and for the data owners to better measure the privacy risk when releasing their data to third parties.
Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene Expression
Authors: Phillips Rob , Belliveau Nathan M. , Chure Griffin , Garcia Hernan G. , Razo-Mejia Manuel , Scholes Clarissa
Published: May 2019

It is tempting to believe that we now own the genome. The ability to read and rewrite it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles’ heel exposed by all of the genomic data that has accrued: We still do not know how to interpret them. Many genes are subject to sophisticated programs of transcriptional regulation, mediated by DNA sequences that harbor binding sites for transcription factors, which can up- or down-regulate gene expression depending upon environmental conditions. This gives rise to an input–output function describing how the level of expression depends upon the parameters of the regulated gene—for instance, on the number and type of binding sites in its regulatory sequence. In recent years, the ability to make precision measurements of expression, coupled with the ability to make increasingly sophisticated theoretical predictions, has enabled an explicit dialogue between theory and experiment that holds the promise of covering this genomic Achilles’ heel. The goal is to reach a predictive understanding of transcriptional regulation that makes it possible to calculate gene expression levels from DNA regulatory sequence. This review focuses on the canonical simple repression motif to ask how well the models that have been used to characterize it actually work. We consider a hierarchy of increasingly sophisticated experiments in which the minimal parameter set learned at one level is applied to make quantitative predictions at the next. We show that these careful quantitative dissections provide a template for a predictive understanding of the many more complex regulatory arrangements found across all domains of life.
Corrupting International Organizations
Authors: Vreeland James Raymond
Published: May 2019

As the world turns against international institutions, this article reviews evidence of the corrupting of global organizations. The review focuses on three international organizations that emerged from World War II: the Bretton Woods institutions [the International Monetary Fund (IMF) and the World Bank] and the United Nations (UN). The article explores evidence of major shareholders (mainly the United States) using the Bretton Woods institutions to funnel money and other favors to strategically preferred countries. Then the review discusses vote buying across a range of issues debated at the UN and finally turns to dark scholarship on the use of UN human rights institutions by autocratic states as a veil to violate those very rights. The article concludes that government pursuit of strategic objectives may be a necessary part of global cooperation, but scholarship should continue to delve into the micro foundations underlying the macro evidence presented here to better inform reformers on how to limit corrupting influences.
The adaptive immune role of metallothioneins in the pathogenesis of diabetic cardiomyopathy: good or bad
Authors: Ge Tingwen , Yu Youxi , Cui Jiuwei , Cai Lu
Published: May 2019

Diabetes is a metabolic disorder characterized by hyperglycemia, resulting in low-grade systemic inflammation. Diabetic cardiomyopathy (DCM) is a common complication among diabetic patients, and the mechanism underlying its induction of cardiac remodeling and dysfunction remains unclear. Numerous experimental and clinical studies have suggested that adaptive immunity, especially T lymphocyte-mediated immunity, plays a potentially important role in the pathogenesis of diabetes and DCM. Metallothioneins (MTs), cysteine-rich, metal-binding proteins, have antioxidant properties. Some potential mechanisms underlying the cardioprotective effects of MTs include the role of MTs in calcium regulation, zinc homeostasis, insulin sensitization, and antioxidant activity. Moreover, metal homeostasis, especially MT-regulated zinc homeostasis, is essential for immune function. This review discusses aberrant immune regulation in diabetic heart disease with respect to endothelial insulin resistance and the effects of hyperglycemia and hyperlipidemia on tissues and the different effects of intracellular and extracellular MTs on adaptive immunity. This review shows that intracellular MTs are involved in naïve T-cell activation and reduce regulatory T-cell (Treg) polarization, whereas extracellular MTs promote proliferation and survival in naïve T cells and Treg polarization but inhibit their activation, thus revealing potential therapeutic strategies targeting the regulation of immune cell function by MTs.
Computational deconvolution of synovial tissue cellular composition: presence of adipocytes in synovial tissue decreased during arthritis pathogenesis and progression
Authors: Wang Wenhui , Wang Li , Gulko Percio S. , Zhu Jun
Published: May 2019

Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common forms of arthritis. The synovial tissue is the major site of inflammation of OA and RA and consists of diverse cells. Synovial tissue cell composition changes during arthritis pathogenesis and progression have not been systematically characterized and may provide critical insights into disease processes. In this study we aimed at systematically examining cellular changes in synovial tissue. Publicly available synovial tissue transcriptomic data sets were used. We computationally estimated cell compositions in synovial tissue based on transcriptomic data and compared cell compositions in different diseases or at different disease stages. Synovial fibroblasts, macrophages, adipocytes, and immune cells were the major cell types in all synovial tissue. Both OA and RA patients had a significantly lower adipocyte fraction compared with healthy controls. The decrease trend was also observed during OA and RA progression. The fraction of monocytes was also increased in both OA and RA arthritis patients, consistent with the observations that inflammation involved in both OA and RA. But the monocyte fraction in RAs was much higher than the ones in healthy controls and OAs. The M2 macrophage fraction was reduced in RA compared with OA, the reduction trend continued during RA progression from the early- to the late-stage. There were consistent cell composition differences between different types or stages of arthritis. Both in RA and OA, the new discovery of changes in the adipocyte and M2 macrophage fractions has potential leading to novel therapeutic development.
How Glyphosate Impairs Liver Condition in the Field Lizard Podarcis siculus (Rafinesque-Schmaltz, 1810): Histological and Molecular Evidence
Authors: Verderame Mariailaria , Scudiero Rosaria
Published: May 2019

The potential toxicity of glyphosate, a widely used broad-spectrum herbicide, is currently a great matter of debate. As vertebrate insectivores, lizards protect plants from herbivorous insects increasing plant biomass via the trophic cascade and represent an important link between invertebrates and higher predators. A negative effect of glyphosate on lizards’ survival could have major impacts at the ecological levels. In this study, we investigated the effects of the exposure to low doses of glyphosate on the liver of the wall lizard Podarcis siculus, a suitable bioindicator of soil pollution. Two different doses of pure glyphosate (0.05 and 0.5 μg/kg body weight) were orally administered every other day for 3 weeks to sexually mature males and females. The results demonstrated that both doses, despite being very low, are toxic for the liver that showed clear signs of suffering, regardless of sex. The histological analysis provided a scenario of severe hepatic condition, which degenerated until the appearance of fibrotic formations. The morphological observations were consistent with a loss of liver physiological functions. Immunocytochemical investigations allowed us to detect an involvement of antioxidant/cytoprotective proteins, such as superoxide dismutase 1 (Cu/Zn SOD, known as SOD1), glutathione peroxidase 1 (GPx1), metallothionein (MT), and tumor suppressor protein 53, (p53) suggesting that the liver was trying to react against stress signals and damage induced by glyphosate. Finally, in situ hybridization and Real-Time PCR analysis showed the upregulation of estrogen receptor α and vitellogenin gene expression, thus demonstrating the xenoestrogenic action of glyphosate. The imbalance of the hormonal homeostasis could threaten the lizards’ reproductive fitness and survival, altering the trophic cascade.
Anesthesia for Open Radical Retropubic Prostatectomy: A Comparison between Combined Spinal Epidural Anesthesia and Combined General Epidural Anesthesia
Authors: Kofler O. , Prueckner S. , Weninger E. , Tomasi R. , Karl A. , Niedermayer S. , Jovanovic A. , Müller H. H. , Stief C. , Zwissler B. , von Dossow V.
Published: May 2019

Background. Several anesthesiologic regimens can be used for open radical retropubic prostatectomy. The aim of this retrospective analysis was to compare the combined general epidural anesthesia and the combined spinal epidural anesthesia with regard to availability, efficacy, side effects, and perioperative time consumption in a high-volume center. Methods. A retrospective analysis was performed by querying the electronic medical records of 1207 consecutive patients from the database of our online documentation software. All patients underwent open radical retropubic prostatectomy from 01/2008 to 08/2011 and met the study criteria. Linear and multivariate regression analyses were performed to identify differences in parameters such as time consumption in the operating unit, hemodynamic parameters, volume replacement, and catecholamine therapy. Results. 698 (57.8%) patients have been undergoing open radical retropubic prostatectomy under combined spinal epidural anesthesia and 509 (42.2%) patients by combined general epidural anesthesia. Operating unit (p <0.0001) and post-anesthesia care unit stay (p <0.0001) as well as total hospital stay (p <0.0001) were significantly shorter in the combined spinal epidural anesthesia group. In addition, this group had reduced intraoperative volume need (p <0.0001) as well as lower need of catecholamines (p <0.0001). Conclusions. This retrospective study suggests that the combined spinal epidural anesthesia seems to be a suitable and efficient anesthesia technique for patients undergoing open radical retropubic prostatectomy. This specific approach reduces time in the operation unit and length of hospital stay.
Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation
Authors: Chai Nannan , Zhang Hao , Li Lingxu , Yu Xue , Liu Yan , Lin Yan , Wang Lina , Yan Jiamin , Nikolaevna Sazonova Elena , Zhao Yajun
Published: May 2019

Intrauterine hypoxia (IUH) is a common intrauterine dysplasia that can cause programming of the offspring cardiovascular system. In this study, we hypothesized that placental treatment with spermidine (SPD) can prevent heart injury in neonatal offspring exposed to IUH. Pregnant rats were exposed to 21% O2 or 10% O2 (hypoxia) for 7 days prior to term or were exposed to hypoxia and intraperitoneally administered SPD or SPD+difluromethylornithine (DFMO) on gestational days 15-21. Seven-day-old offspring were then sacrificed to assess several parameters. Our results demonstrated that IUH led to decreased myocardial ornithine decarboxylase (ODC) and increased spermidine/spermine N1-acetyltransferase (SSAT) expression in the offspring. IUH also resulted in decreased offspring body weight, heart weight, cardiomyocyte proliferation, and antioxidant capacity and increased cardiomyocyte apoptosis and fibrosis. Furthermore, IUH caused mitochondrial structure abnormality, dysfunction, and decreased biogenesis and led to a fission/fusion imbalance in offspring hearts. In vitro, hypoxia induced mitochondrial ROS accumulation, decreased membrane potential, and increased fragmentation. Notably, all hypoxia-induced changes analyzed in this study were prevented by SPD. Thus, in utero SPD treatment is a potential strategy for preventing IUH-induced neonatal cardiac injury.
TRPA1 Promotes Cardiac Myofibroblast Transdifferentiation after Myocardial Infarction Injury via the Calcineurin-NFAT-DYRK1A Signaling Pathway
Authors: Li Shuang , Sun Xiongshan , Wu Hao , Yu Peng , Wang Xin , Jiang Zhenhua , Gao Erhe , Chen Jiangwei , Li De , Qiu Chenming , Song Baomei , Chen Ken , He Kecheng , Yang Dachun , Yang Yongjian
Published: May 2019

Cardiac fibroblasts (CFs) are a critical cell population responsible for myocardial extracellular matrix homeostasis. After stimulation by myocardial infarction (MI), CFs transdifferentiate into cardiac myofibroblasts (CMFs) and play a fundamental role in the fibrotic healing response. Transient receptor potential ankyrin 1 (TRPA1) channels are cationic ion channels with a high fractional Ca2+ current, and they are known to influence cardiac function after MI injury; however, the molecular mechanisms regulating CMF transdifferentiation remain poorly understood. TRPA1 knockout mice, their wild-type littermates, and mice pretreated with the TRPA1 agonist cinnamaldehyde (CA) were subjected to MI injury and monitored for survival, cardiac function, and fibrotic remodeling. TRPA1 can drive myofibroblast transdifferentiation initiated 1 week after MI injury. In addition, we explored the underlying mechanisms via in vitro experiments through gene transfection alone or in combination with inhibitor treatment. TRPA1 overexpression fully activated CMF transformation, while CFs lacking TRPA1 were refractory to transforming growth factor β- (TGF-β-) induced transdifferentiation. TGF-β enhanced TRPA1 expression, which promoted the Ca2+-responsive activation of calcineurin (CaN). Moreover, dual-specificity tyrosine-regulated kinase-1a (DYRK1A) regulated CaN-mediated NFAT nuclear translocation and TRPA1-dependent transdifferentiation. These findings suggest a potential therapeutic role for TRPA1 in the regulation of CMF transdifferentiation in response to MI injury and indicate a comprehensive pathway driving CMF formation in conjunction with TGF-β, Ca2+ influx, CaN, NFATc3, and DYRK1A.
Long-Term Follow-Up following Condylotomy in a Case of Traumatic Unilateral Anterosuperior Mandibular Condyle Dislocation
Authors: Nabil Syed , Kuppusamy Elavarasi , Nordin Rifqah , Nazimi Abdul Jabar , Ramli Roszalina
Published: May 2019

Anterosuperior temporomandibular joint dislocation is rare. Manual reduction of such dislocation is difficult especially when treatment is delayed. Therefore, it has an increased likelihood of needing surgical intervention to achieve reduction. The authors report a case of an anterosuperior temporomandibular dislocation in a 19-year-old male following a motor vehicle accident. Difficulties were encountered in reducing the dislocation necessitating surgically assisted reduction. The long-term outcome following management by condylotomy is reported. This present report also reviews the literature regarding the classification and management of this uncommon dislocation.