bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper Ions and Coordination Complexes as Novel Carbapenem Adjuvants
Authors: Djoko Karrera Y. , Achard Maud E. S. , Phan Minh-Duy , Lo Alvin W. , Miraula Manfredi , Prombhul Sasiprapa , Hancock Steven J. , Peters Kate M. , Sidjabat Hanna E. , Harris Patrick N. , Mitić Nataša , Walsh Timothy R. , Anderson Gregory J. , Shafer William M. , Paterson David L. , Schenk Gerhard , McEwan Alastair G. , Schembri Mark A.
Published: November 2017

Carbapenem-resistantEnterobacteriaceaeare urgent threats to global human health. These organisms produce β-lactamases with carbapenemase activity, such as the metallo-β-lactamase NDM-1, which is notable due to its association with mobile genetic elements and the lack of a clinically useful inhibitor. Here we examined the ability of copper to inhibit the activity of NDM-1 and explored the potential of a copper coordination complex as a mechanism to efficiently deliver copper as an adjuvant in clinical therapeutics. An NDM-positiveEscherichia coliisolate, MS6192, was cultured from the urine of a patient with a urinary tract infection. MS6192 was resistant to antibiotics from multiple classes, including diverse β-lactams (penicillins, cephalosporins, and carbapenems), aminoglycosides, and fluoroquinolones. In the presence of copper (range, 0 to 2 mM), however, the susceptibility of MS6192 to the carbapenems ertapenem and meropenem increased markedly. In standard checkerboard assays, copper decreased the MICs of ertapenem and meropenem against MS6192 in a dose-dependent manner, suggesting a synergistic mode of action. To examine the inhibitory effect of copper in the absence of other β-lactamases, theblaNDM-1gene from MS6192 was cloned and expressed in a recombinantE. coliK-12 strain. Analysis of cell extracts prepared from this strain revealed that copper directly inhibited NDM-1 activity, which was confirmed using purified recombinant NDM-1. Finally, delivery of copper at a low concentration of 10 μM by using the FDA-approved coordination complex copper-pyrithione sensitized MS6192 to ertapenem and meropenem in a synergistic manner. Overall, this work demonstrates the potential use of copper coordination complexes as novel carbapenemase adjuvants.
Comparison of preservation and transportation protocols for preloaded Descemet membrane endothelial keratoplasty
Authors: Romano Vito , Parekh Mohit , Ruzza Alessandro , Willoughby Colin E , Ferrari Stefano , Ponzin Diego , Kaye Stephen B , Levis Hannah J
Published: November 2017

Background/aims

Descemet membrane endothelial keratoplasty (DMEK) preparation is technically demanding and is a limiting factor for uptake of this kind of surgery. Supply methods that simplify the procedure for surgeons are key to increasing uptake. This study compares two different shipping protocols for DMEK.

Methods

An 8.5 mm DMEK graft was punched, marked and loaded for transportation in two different conditions: (A) endothelium trifolded inwards in organ culture conditions (n=7) and (B) endothelium rolled outwards in hypothermic conditions (n=7). Tissues were shipped from Italy to the UK, then analysed for orientation, endothelial cell density, denuded areas, cell mortality, triple viability staining (Hoechst/ethidium homodimer/calcein AM (HEC)), immunolocalisation of ZO-1 and Na/K-ATPase proteins, visualisation of actin filaments using phalloidin and histological analysis using H&E on paraffin-embedded sections.

Results

All tissues clearly showed the mark used for graft orientation. After shipping in condition A, there was an increase in cell mortality of 8.1% and in denuded areas of 22.4%, whereas for condition B there was an increase in cell mortality of 14.2% and in denuded areas of 34.3% after shipping. HEC staining revealed areas of viable cells and apoptotic cells, with large denuded areas found in the periphery for condition B and within folds for condition A.

Conclusions

Prestripped preloaded DMEK grafts retained sufficient viable cells for transplantation, with condition A (endothelium-in) offering the advantage of greater flexibility of use due to a longer shelf-life. HEC analysis provides further detailed information as to the status of DMEK grafts and should be used in future similar studies.
Exploring perceptions and experiences of patients who have chronic pain as state prescription opioid policies change: a qualitative study in Indiana
Authors: Al Achkar Morhaf , Revere Debra , Dennis Barbara , MacKie Palmer , Gupta Sumedha , Grannis Shaun
Published: November 2017

Objectives

The misuse and abuse of prescription opioids (POs) is an epidemic in the USA today. Many states have implemented legislation to curb the use of POs resulting from inappropriate prescribing. Indiana legislated opioid prescribing rules that went into effect in December 2013. The rules changed how chronic pain is managed by healthcare providers. This qualitative study aims to evaluate the impact of Indiana’s opioid prescription legislation on the patient experiences around pain management.

Setting

This is a qualitative study using interviews of patient and primary care providers to obtain triangulated data sources. The patients were recruited from an integrated pain clinic to which chronic pain patients were referred from federally qualified health clinics (FQHCs). The primacy care providers were recruited from the same FQHCs. The study used inductive, emergent thematic analysis.

Participants

Nine patient participants and five primary care providers were included in the study.

Results

Living with chronic pain is disruptive to patients’ lives on multiple dimensions. The established pain management practices were disrupted by the change in prescription rules. Patient–provider relationships, which involve power dynamics and decision making, shifted significantly in parallel to the rule change.

Conclusions

As a result of the changes in pain management practice, some patients experienced significant challenges. Further studies into the magnitude of this change are necessary. In addition, exploring methods for regulating prescribing while assuring adequate access to pain management is crucial.
Site-specific cancer mortality inequalities by employment and occupational groups: a cohort study among Belgian adults, 2001–2011
Authors: Vanthomme Katrien , Van den Borre Laura , Vandenheede Hadewijch , Hagedoorn Paulien , Gadeyne Sylvie
Published: November 2017

Objective

This study probes into site-specific cancer mortality inequalities by employment and occupational group among Belgians, adjusted for other indicators of socioeconomic (SE) position.

Design

This cohort study is based on record linkage between the Belgian censuses of 1991 and 2001 and register data on emigration and mortality for 01/10/2001 to 31/12/2011.

Setting

Belgium.

Participants

The study population contains all Belgians within the economically active age (25–65 years) at the census of 1991.

Outcome measures

Both absolute and relative measures were calculated. First, age-standardised mortality rates have been calculated, directly standardised to the Belgian population. Second, mortality rate ratios were calculated using Poisson’s regression, adjusted for education, housing conditions, attained age, region and migrant background.

Results

This study highlights inequalities in site-specific cancer mortality, both related to being employed or not and to the occupational group of the employed population. Unemployed men and women show consistently higher overall and site-specific cancer mortality compared with the employed group. Also within the employed group, inequalities are observed by occupational group. Generally manual workers and service and sales workers have higher site-specific cancer mortality rates compared with white-collar workers and agricultural and fishery workers. These inequalities are manifest for almost all preventable cancer sites, especially those cancer sites related to alcohol and smoking such as cancers of the lung, oesophagus and head and neck. Overall, occupational inequalities were less pronounced among women compared with men.

Conclusions

Important SE inequalities in site-specific cancer mortality were observed by employment and occupational group. Ensuring financial security for the unemployed is a key issue in this regard. Future studies could also take a look at other working regimes, for instance temporary employment or part-time employment and their relation to health.
Testosterone in advance age: a New Zealand longitudinal cohort study: Life and Living in Advanced Age (Te Puāwaitanga o Ngā Tapuwae Kia Ora Tonu)
Authors: Connolly Martin J , Kerse Ngaire , Wilkinson Tim , Menzies Oliver , Rolleston Anna , Chong Yih Harng , Broad Joanna B , Moyes Simon A , Jatrana Santosh , Teh Ruth
Published: November 2017

Objectives

Serum testosterone (T) levels in men decline with age. Low T levels are associated with sarcopenia and frailty in men aged>80 years. T levels have not previously been directly associated with disability in older men. We explored associations between T levels, frailty and disability in a cohort of octogenarian men.

Setting

Data from all men from Life and Living in Advanced Age Cohort Study in New Zealand, a longitudinal cohort study in community-dwelling older adults.

Participants

Community-dwelling (>80 years) adult men excluding those receiving T treatment or with prostatic carcinoma.

Outcomes measures

Associations between baseline total testosterone (TT) and calculated free testosterone (fT), frailty (Fried scale) and disability (Nottingham Extended Activities of Daily Living scale (NEADL)) (baseline and 24 months) were examined using multivariate regression and Wald’s χ2techniques. Subjects with the lowest quartile of baseline TT and fT values were compared with those in the upper three quartiles.

Results

Participants: 243 men, mean (SD) age 83.7 (2.0) years. Mean (SD) TT=17.6 (6.8) nmol/L and fT=225.3 (85.4) pmol/L. On multivariate analyses, lower TT levels were associated with frailty: β=0.41, p=0.017, coefficient of determination (R2)=0.10 and disability (NEADL) (β=−1.27, p=0.017, R2=0.11), low haemoglobin (β=−7.38, p=0.0016, R2=0.05), high fasting glucose (β=0.38, p=0.038, R2=0.04) and high C reactive protein (CRP) (β=3.57, p=0.01, R2=0.06). Low fT levels were associated with frailty (β=0.39, p=0.024, R2=0.09) but not baseline NEADL (β=−1.29, p=0.09, R2=0.09). Low fT was associated with low haemoglobin (β=−7.83, p=0.0008, R2=0.05) and high CRP (β=2.86, p=0.04, R2=0.05). Relationships between baseline TT and fT, and 24-month outcomes of disability and frailty were not significant.

Conclusions

In men over 80 years, we confirm an association between T levels and baseline frailty scores. The new finding of association between T levels and disability is potentially relevant to debates on T supplementation in older men, though, as associations were not present at 24 months, further work is needed.
Association between visceral obesity and hepatitis C infection stratified by gender: a cross-sectional study in Taiwan
Authors: Tsao Yu-Chung , Chen Jau-Yuan , Yeh Wei-Chung , Peng Yun-Shing , Li Wen-Cheng
Published: November 2017

Objectives

The global prevalence of hepatitis C virus (HCV) is approximately 2%–3%, and the prevalence of the positive anti-HCV antibody has been increasing. Several studies have evaluated regional adipose tissue distribution and metabolism over the past decades. However, no study has focused on the gender difference in visceral obesity among patients with HCV infection.

Design

Retrospective cross-sectional study.

Setting

We reviewed the medical records of patients who visited a hospital in Southern Taiwan for health check-up from 2013 to 2015.

Participants

A total of 1267 medical records were collected. We compared patient characteristics, variables related to metabolic risk and body composition measured using bioelectrical impedance analysis between the groups. Regression models were built to adjust for possible confounding factors.

Results

The prevalence rate of the positive anti-HCV antibody was 8.8% in the study population, 8.5% in men and 9.2% in women. Men with HCV infection tended to be older and have lower total cholesterol levels and higher alanine aminotransferase (ALT) levels (p<0.001). Women with HCV infection tended to be older and have higher levels of fasting glucose and ALT (p<0.001). After adjusting for confounding factors, body fat percentage, fat-free mass/body weight (BW) and muscle mass/BW were found to be the independent determinants of visceral obesity in patients without HCV infection (p<0.001). However, the trend was not such obvious in patients with HCV infection, though still statistically significant (p<0.05). Furthermore, the trend was less significant in men with HCV infection.

Conclusions

The findings suggested that HCV modulates host lipid metabolism and distribution to some extent, and a gender difference was also noted.
Effect of an intensive 3-week preoperative home rehabilitation programme in patients with chronic obstructive pulmonary disease eligible for lung cancer surgery: a multicentre randomised controlled trial
Authors: Laurent Hélène , Galvaing Géraud , Thivat Emilie , Coudeyre Emmanuel , Aubreton Sylvie , Richard Ruddy , Kwiatkowski Fabrice , Costes Frederic , Filaire Marc
Published: November 2017

Introduction

Surgery is the standard curative treatment for lung cancer but is only possible in patients with local tumour and preserved exercise capacity. Improving fitness before surgery can reduce postoperative complications and mortality. However, preoperative rehabilitation remains difficult to implement for several reasons. We aim to investigate the effectiveness of an intensive 3-week home-based preoperative exercise training programme on hospital discharge ability, postoperative complications and physical performance in patients with chronic obstructive pulmonary disease (COPD) who are eligible for lung cancer surgery.

Methods and analysis

We designed a multicentre randomised controlled trial. The randomisation sequence will be generated and managed electronically by a research manager independent of assessments or interventions. We will recruit 90 patients with COPD and a diagnosis of lung cancer from four university hospitals. The rehabilitation group (R group) will receive a standardised preoperative home exercise programme for 3 weeks, combining both high-intensity training and usual physical therapy. The R group will perform 15 training sessions over 3 weeks on a cycloergometer. A physical therapist experienced in pulmonary rehabilitation will visit the patient at home and supervise one session a week. The R group will be compared with a control group receiving preoperative usual physical therapy only. The primary outcome will be hospital discharge ability assessed with a 10-item list. Secondary outcomes will be postoperative course (complication rate and mortality) as well as pulmonary function, exercise capacity and quality of life assessed 1 month before and the day before surgery.

Ethics and dissemination

This protocol has been approved by the French health authority for research (2016-A00622-49) and the research ethics committee/institutional review board (AU1267). Adverse events that occur during the protocol will be reported to the principal investigator. The results will be published in an international peer-reviewed journal.

Trial registration number

NCT03020251.
Characteristics and healthcare utilisation patterns of high-cost beneficiaries in the Netherlands: a cross-sectional claims database study
Authors: Wammes Joost Johan Godert , Tanke Marit , Jonkers Wilma , Westert Gert P , Van der Wees Philip , Jeurissen Patrick PT
Published: November 2017

Objective

To determine medical needs, demographic characteristics and healthcare utilisation patterns of the top 1% and top 2%–5% high-cost beneficiaries in the Netherlands.

Design

Cross-sectional study using 1 year claims data. We broke down high-cost beneficiaries by demographics, the most cost-incurring condition per beneficiary and expensive treatment use.

Setting

Dutch curative health system, a health system with universal coverage.

Participants

4.5 million beneficiaries of one health insurer.

Measures

Annual total costs through hospital, intensive care unit use, expensive drugs, other pharmaceuticals, mental care and others; demographics; most cost-incurring and secondary conditions; inpatient stay; number of morbidities; costs per ICD10-chapter (International Statistical Classification of Diseases, 10th revision); and expensive treatment use (including dialysis, transplant surgery, expensive drugs, intensive care unit and diagnosis-related groups >€30 000).

Results

The top 1% and top 2%–5% beneficiaries accounted for 23% and 26% of total expenditures, respectively. Among top 1% beneficiaries, hospital care represented 76% of spending, of which, respectively, 9.0% and 9.1% were spent on expensive drugs and ICU care. We found that 54% of top 1% beneficiaries were aged 65 years or younger and that average costs sharply decreased with higher age within the top 1% group. Expensive treatments contributed to high costs in one-third of top 1% beneficiaries and in less than 10% of top 2%–5% beneficiaries. The average number of conditions was 5.5 and 4.0 for top 1% and top 2%–5% beneficiaries, respectively. 53% of top 1% beneficiaries were treated for circulatory disorders but for only 22% of top 1% beneficiaries this was their most cost-incurring condition.

Conclusions

Expensive treatments, most cost-incurring condition and age proved to be informative variables for studying this heterogeneous population. Expensive treatments play a substantial role in high-costs beneficiaries. Interventions need to be aimed at beneficiaries of all ages; a sole focus on the elderly would leave many high-cost beneficiaries unaddressed. Tailored interventions are needed to meet the needs of high-cost beneficiaries and to avoid waste of scarce resources.
Ratings game: an analysis of Nursing Home Compare and Yelp ratings
Authors: Johari Kayla , Kellogg Caitlyn , Vazquez Katalina , Irvine Krystle , Rahman Anna , Enguidanos Susan
Published: November 2017

Background

Two strategies for rating the quality of nursing homes (NHs) in the USA are exemplified by the Nursing Home Compare (NHC) website, launched by the federal Centers for Medicare and Medicaid Services in 1998, and Yelp.com, an online consumer review site that has grown in popularity since its founding in 2004. Both sites feature a 5-star rating system. While much is known about NHC ratings, little is known about NH Yelp ratings. This study examines Yelp ratings for NHs in California and compares these ratings with NHC ratings. Understanding how these ratings relate can inform efforts to empower consumers and enhance NH decision-making.

Methods

We collected NHC and Yelp ratings for all California NHs between September and November 2016. For each NH with a Yelp review, we recorded the star rating and the total number of reviews. We also recorded the NHC 5-star rating and NHC ratings for inspections, staffing and quality measures (QMs). We conducted descriptive statistics and frequencies for these variables. We conducted correlations and tested means to compare the ratings.

Results

A total of 675 NHs (68.1% of the total sample of 991 NHs) had both Yelp ratings and NHC ratings. Correlations between the Yelp and NHC ratings were relatively weak. The Yelp rating was significantly lower than the 5-star NHC rating and the NHC ratings for staffing and QMs. It was significantly higher than the NHC inspection rating.

Conclusions

This study found that when consumers rate NHs on Yelp, their ratings differ considerably from NHC ratings, a finding in keeping with similar studies of NH quality measurement. Further research is needed to analyse the content of Yelp reviews and compare the themes and topics consumers identify with those reported on NHC.
Identification of S1 and S2 Heart Sound Patterns Based on Fractal Theory and Shape Context
Authors: Gavrovska Ana , Zajić Goran , Bogdanović Vesna , Reljin Irini , Reljin Branimir
Published: November 2017

There has been a sustained effort in the research community over the recent years to develop algorithms that automatically analyze heart sounds. One of the major challenges is identifying primary heart sounds, S1 and S2, as they represent reference events for the analysis. The study presented in this paper analyzes the possibility of improving the structure characterization based on shape context and structure assessment using a small number of descriptors. Particularly, for the primary sound characterization, an adaptive waveform filtering is applied based on blanket fractal dimension for each preprocessed sound candidate belonging to pediatric subjects. This is followed by applying the shape based methods selected for the structure assessment of primary heart sounds. Different methods, such as the fractal ones, are used for the comparison. The analysis of heart sound patterns is performed using support vector machine classifier showing promising results (above 95% accuracy). The obtained results suggest that it is possible to improve the identification process using the shape related methods which are rarely applied. This can be helpful for applications involving automatic heart sound analysis.
Low Altitude UAV Air-to-Ground Channel Measurement and Modeling in Semiurban Environments
Authors: Qiu Zhihong , Chu Xi , Calvo-Ramirez Cesar , Briso César , Yin Xuefeng
Published: November 2017

Small- and medium-sized unmanned aerial vehicles (UAVs) can fly for a short distance (<2 km) from a control station in a nonsegregated air space (altitudes < 100 m). It is of great interest to model the propagation channel under such condition, where there is an important influence from the environment. This paper presents multiple measurements carried out in low altitudes with a medium-sized UAV flying over a semiurban environment. Path loss exponent is given based on the measurements done at different altitudes and a height-dependent Rician K factor model is proposed. The results clearly reveal the existence of two propagation zones with very distinct channel characteristics. The breakpoint indicates the height where the condition of the channel changes rapidly. At low altitudes, the obstacles generate a large amount of multipath and the propagation is greatly affected, while at higher altitudes the influence mitigates. Our results are useful for the modeling of low altitude air-to-ground (AG) propagation channels and the performance analysis of UAV-enabling AG communication systems, such as the channel capacity and the throughput.
Protective Effects of Genistein against Mono-(2-ethylhexyl) Phthalate-Induced Oxidative Damage in Prepubertal Sertoli Cells
Authors: Zhang Liandong , Gao Ming , Zhang Tongdian , Chong Tie , Wang Ziming , Zhai Xiaoqiang , Wu Zhizhong , Li Hecheng
Published: November 2017

Mono-(2-ethylhexyl) phthalate (MEHP) and genistein are two of the most prevalent endocrine-disrupting chemicals (EDCs) that present in the environment and food. However, how these two EDCs would affect prepubertal Sertoli cells development was rarely studied. In this study, primary prepubertal Sertoli cells were isolated from 22-day-old Sprague Dawley rats and exposed to MEHP at 1 μmol/L, 10 μmol/L, and 100 μmol/L (M1, M10, and M100), genistein at 10 μmol/L (G), and their combination (G + M1, G + M10, and G + M100). Cell proliferation inhibition rate, apoptosis and necrosis rate, and cellular redox state were evaluated. Our results revealed that MEHP could significantly increase cell proliferation inhibition rate, apoptosis rate, necrosis rate, and intracellular reactive oxidative species level. However, coadministration of genistein could partially alleviate MEHP-induced prepubertal Sertoli cells oxidative injuries via enhancement of testicular antioxidative enzymes activities and upregulation of Nrf2 and HO-1, indicating that genistein could partially attenuate MEHP-induced prepubertal Sertoli cells damage through antioxidative action and may have promising future on its curative role for attenuating other EDCs-induced reproductive disorders.
Genital Tract Infections in an Isolated Community: 100 Women of the Príncipe Island
Authors: Vieira-Baptista Pedro , Grinceviciene Svitrigaile , Bellen Gert , Sousa Carlos , Saldanha Conceição , Broeck Davy Vanden , Bogers John-Paul , Donders Gilbert
Published: November 2017

Objective. To characterize the vaginal microbiome and the rate of sexually transmitted infections (STIs) in the women of Príncipe (São Tomé and Príncipe). Methods. Cross-sectional study of 100 consecutive women, invited for a free appointment and cervical cancer screening. A vaginal slide (wet mount microscopy) and a cervical sample (ThinPrep®) (Pap test, high risk human papillomavirus [HR-HPV], N. gonorrhea [NG], T. vaginalis [TV], and C. trachomatis [CT]) were obtained. Results. TV, NG, CT, and HIV were found in 8.0%, 2.0%, 3.0%, and 2.0%, respectively, and were more prevalent in younger women. HR-HPV was positive in 36.7%; 2 were positive for HPV18, but none for HPV16. Coinfection of HPV with other STIs was 8.3%. Prevalence of abnormal vaginal flora (AVF) was 82.5%, mostly bacterial vaginosis (BV) 54.6%, and moderate/severe aerobic vaginitis (msAV) 25.8%. HR-HPV was not related to BV (p=0.67). The association of abnormal Pap test with msAV was not significant (p=0.08). Conclusion. The prevalence of NG, CT, TV, and HR-HPV was according to expected, while that of HR-AVF was higher. The surprisingly low prevalence of HPV16 and HPV18 must be considered in the design of programs for prevention and vaccination; this setting can be useful as a model for postvaccination scenarios.
One-Pot Aqueous Synthesis of Fluorescent Ag-In-Zn-S Quantum Dot/Polymer Bioconjugates for Multiplex Optical Bioimaging of Glioblastoma Cells
Authors: Mansur Alexandra A. P. , Mansur Herman S. , Carvalho Sandhra M. , Caires Anderson J.
Published: November 2017

Cancer research has experienced astonishing advances recently, but cancer remains a major threat because it is one of the leading causes of death worldwide. Glioblastoma (GBM) is the most malignant brain tumor, where the early diagnosis is vital for longer survival. Thus, this study reports the synthesis of novel water-dispersible ternary AgInS2 (AIS) and quaternary AgInS2-ZnS (ZAIS) fluorescent quantum dots using carboxymethylcellulose (CMC) as ligand for multiplexed bioimaging of malignant glioma cells (U-87 MG). Firstly, AgInS2 core was prepared using a one-pot aqueous synthesis stabilized by CMC at room temperature and physiological pH. Then, an outer layer of ZnS was grown and thermally annealed to improve their optical properties and split the emission range, leading to core-shell alloyed nanostructures. Their physicochemical and optical properties were characterized, demonstrating that luminescent monodispersed AIS and ZAIS QDs were produced with average sizes of 2.2 nm and 4.3 nm, respectively. Moreover, the results evidenced that they were cytocompatible using in vitro cell viability assays towards human embryonic kidney cell line (HEK 293T) and U-87 MG cells. These AIS and ZAIS successfully behaved as fluorescent nanoprobes (red and green, resp.) allowing multiplexed bioimaging and biolabeling of costained glioma cells using confocal microscopy.
Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat
Authors: Xu Shunjun , Yu Jiejing , Zhan Jingjing , Yang Liu , Guo Longgang , Xu Yijuan
Published: November 2017

Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese medicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and there are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue distribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray ionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues collected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg (corresponding to 42 mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as internal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in rat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference. Moreover, in vivo metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in different time periods after oral and intramuscular administration of icariin. In vivo metabolic pathways were involved in hydrolysis, demethylation, oxidation, and conjugation. The preclinical data would be useful for fully understanding in vivo disposition of this compound and interpreting the mechanism of its biological response.
Effect of Package Film on the Quality of Postharvest Chinese Toon Tender Shoots Storage
Authors: Zhu Yongqing , Gao Jia
Published: November 2017

The young leaves and shoots of the Toona sinensis (A. Juss.) Roem. tree, called Chinese toon, are commonly eaten as a vegetable in China. This study was conducted to develop a modified atmosphere packaging (MAP) system for Chinese toon tender shoots and to evaluate the effect of film oxygen transmission rate (OTR) on package atmospheres and consequent product quality changes during storage. Fresh precooled Chinese toon tender shoots (25±0.5 g each) were packaged in sealed 10 cm × 15 cm polyethylene bags prepared with films of OTRs of 8.0, 11.6, 16.6, 21.4, or 29.5 pmol s−1 m−2 Pa−1 and stored at 4±0.5°C for 25 days. Evaluations included package atmospheres, tissue electrolyte leakage, color, and sensory attributes (overall visual quality, off-odor, texture, and marketability). Results indicated that the OTR of the package film significantly (P<0.05) affected package headspace gas composition, a⁎, hue angles, product quality, and shelf-life, under the tested package configurations and storage conditions. Packages with film OTR of 21.4 pmol s−1 m−2 Pa−1 attained stable O2 (8.4–10.0 kPa) and CO2 (2.2–3.0 kPa) levels by day 10, which were maintained through the end of storage; products stored in these packages maintained freshness with high overall quality scores.
An Edge Correlation Based Differentially Private Network Data Release Method
Authors: Lu Junling , Cai Zhipeng , Wang Xiaoming , Zhang Lichen , Duan Zhuojun
Published: November 2017

Differential privacy (DP) provides a rigorous and provable privacy guarantee and assumes adversaries’ arbitrary background knowledge, which makes it distinct from prior work in privacy preserving. However, DP cannot achieve claimed privacy guarantees over datasets with correlated tuples. Aiming to protect whether two individuals have a close relationship in a correlated dataset corresponding to a weighted network, we propose a differentially private network data release method, based on edge correlation, to gain the tradeoff between privacy and utility. Specifically, we first extracted the Edge Profile (PF) of an edge from a graph, which is transformed from a raw correlated dataset. Then, edge correlation is defined based on the PFs of both edges via Jenson-Shannon Divergence (JS-Divergence). Secondly, we transform a raw weighted dataset into an indicated dataset by adopting a weight threshold, to satisfy specific real need and decrease query sensitivity. Furthermore, we propose ϵ-correlated edge differential privacy (CEDP), by combining the correlation analysis and the correlated parameter with traditional DP. Finally, we propose network data release (NDR) algorithm based on the ϵ-CEDP model and discuss its privacy and utility. Extensive experiments over real and synthetic network datasets show the proposed releasing method provides better utilities while maintaining privacy guarantee.
PaTAVTT: A Hardware-in-the-Loop Scaled Platform for Testing Autonomous Vehicle Trajectory Tracking
Authors: Xu Zhigang , Wang Mingliang , Zhang Fengzhi , Jin Sheng , Zhang Jin , Zhao Xiangmo
Published: November 2017

With the advent of autonomous vehicles, in particular its adaptability to harsh conditions, the research and development of autonomous vehicles attract significant attention by not only academia but also practitioners. Due to the high risk, high cost, and difficulty to test autonomous vehicles under harsh conditions, the hardware-in-the-loop (HIL) scaled platform has been proposed as it is a safe, inexpensive, and effective test method. This platform system consists of scaled autonomous vehicle, scaled roadway, monitoring center, transmission device, positioning device, and computers. This paper uses a case of the development process of tracking control for high-speed U-turn to build the tracking control function. Further, a simplified vehicle dynamics model and a trajectory tracking algorithm have been considered to build the simulation test. The experiment results demonstrate the effectiveness of the HIL scaled platform.
Using Emotions in Intelligent Virtual Environments: The EJaCalIVE Framework
Authors: Rincon Jaime A. , Costa Angelo , Novais Paulo , Julian Vicente , Carrascosa Carlos
Published: November 2017

Nowadays, there is a need to provide new applications which allow the definition and implementation of safe environments that attends to the user needs and increases their wellbeing. In this sense, this paper introduces the EJaCalIVE framework which allows the creation of emotional virtual environments that incorporate agents, eHealth related devices, human actors, and emotions projecting them virtually and managing the interaction between all the elements. In this way, the proposed framework allows the design and programming of intelligent virtual environments, as well as the simulation and detection of human emotions which can be used for the improvement of the decision-making processes of the developed entities. The paper also shows a case study that enforces the need of this framework in common environments like nursing homes or assisted living facilities. Concretely, the case study proposes the simulation of a residence for the elderly. The main goal is to have an emotion-based simulation to train an assistance robot avoiding the complexity involved in working with the real elders. The main advantage of the proposed framework is to provide a safe environment, that is, an environment where users are able to interact safely with the system.
MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183
Authors: Zhang Yuan-Yuan , Feng Hao-Miao
Published: November 2017

Background/Aims: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously. Methods: The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay. Results: MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells. Conclusion: This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.
Quaking Inhibits Doxorubicin-Mediated Cardiotoxicity Through Regulation of Cardiac Circular RNA Expression
Authors: Gupta Shashi Kumar , Garg Ankita , Bär Christian , Chatterjee Shambhabi , Foinquinos Ariana , Milting Hendrik , Streckfuß-Bömeke Katrin , Fiedler Jan , Thum Thomas
Published: November 2017

Rationale:

RBPs (RNA-binding proteins) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs.

Objective:

We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function.

Methods and Results:

Global transcriptome profiling from murine myocardium exposed to doxorubicin identified 5 differentially expressed RBPs. Expression of the RBP QKI (Quaking) in response to doxorubicin was strongly downregulated in rodent cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes in vitro and in vivo in mice. Knockdown of
Qki
in primary cardiomyocytes increased apoptosis and atrophy after treatment with doxorubicin, whereas lentiviral mediated overexpression of
Qki5
inhibited the doxorubicin-induced apoptosis in cardiomyocytes. In vivo, AAV9 (adeno-associated virus serotype 9)–mediated cardiac overexpression of
Qki5
prevented cardiac apoptosis and cardiac atrophy induced by doxorubicin and improved cardiac function. Mechanistically, by lentiviral-based overexpression and CRISPR/Cas9-mediated silencing of
Qki5
, we identified regulated expression of specific circular RNAs derived from
Ttn
(Titin),
Fhod3
(Formin homology 2 domain containing 3), and
Strn3
(Striatin, calmodulin-binding protein 3). Moreover, inhibition of
Ttn
-derived circular RNA increased the susceptibility of cardiomyocytes to doxorubicin.

Conclusions:

We here show that overexpression of
Qki5
strongly attenuates the toxic effect of doxorubicin via regulating a set of circular RNAs.
Qki5
is, thus, an interesting target molecule to combat doxorubicin-induced cardiotoxicity.
Effects of Bariatric Surgery in Obese Patients With Hypertension
Authors: Schiavon Carlos Aurelio , Bersch-Ferreira Angela Cristine , Santucci Eliana Vieira , Oliveira Juliana Dantas , Torreglosa Camila Ragne , Bueno Priscila Torres , Frayha Julia Caldas , Santos Renato Nakagawa , Damiani Lucas Petri , Noujaim Patricia Malvina , Halpern Helio , Monteiro Frederico L.J. , Cohen Ricardo Vitor , Uchoa Carlos H. , de Souza Marcio Gonçalves , Amodeo Celso , Bortolotto Luiz , Ikeoka Dimas , Drager Luciano F. , Cavalcanti Alexandre Biasi , Berwanger Otavio
Published: November 2017

Background:

Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed.

Methods:

In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m
2
. Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm Hg and 90 mm Hg, respectively, at 12 months.

Results:

We included 100 patients (76% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1–14.0;
P
<0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4–10.6;
P
=0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group.

Conclusions:

Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01784848.
Selective Nanoparticle Targeting of the Renal Tubules
Authors: Williams Ryan M. , Shah Janki , Tian Helen S. , Chen Xi , Geissmann Frederic , Jaimes Edgar A. , Heller Daniel A.
Published: November 2017

Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases.
Three-Month Endothelial Human Endothelin-1 Overexpression Causes Blood Pressure Elevation and Vascular and Kidney Injury
Authors: Coelho Suellen C. , Berillo Olga , Caillon Antoine , Ouerd Sofiane , Fraulob-Aquino Júlio C. , Barhoumi Tlili , Offermanns Stefan , Paradis Pierre , Schiffrin Ernesto L.
Published: November 2017

Endothelium-derived endothelin (ET)-1 has been implicated in the development of hypertension and end-organ damage, but its exact role remains unclear. We have shown that tamoxifen-inducible endothelium-restricted human ET-1 overexpressing (ieET-1) mice exhibited blood pressure rise after a 3-week induction in an ET type A (ET
A
) receptor-dependent manner, in absence of vascular and renal injury. It is unknown whether long-term ET-1 overexpression results in sustained blood pressure elevation and vascular and renal injury. Adult male ieET-1 and control tamoxifen-inducible endothelium-restricted Cre recombinase (ieCre) mice were induced with tamoxifen and 2.5 months later, were treated with or without the ET
A
receptor blocker atrasentan for 2 weeks. Three-month induction of endothelial human ET-1 overexpression increased blood pressure (
P
<0.01), reduced renal artery flow (
P
<0.001), and caused mesenteric small artery stiffening (
P
<0.05) and endothelial dysfunction (
P
<0.01). These changes were accompanied by enhanced mesenteric small artery
Col1A1
and
Col3A1
expression, and perivascular adipose tissue oxidative stress (
P
<0.05) and monocyte/macrophage infiltration (
P
<0.05). Early renal injury was demonstrated by increased kidney injury molecule-1 expression in renal cortex tubules (
P
<0.05), with, however, undetectable lesions using histochemistry staining and unchanged urinary albumin. There was associated increased myeloid (CD11b
+
) and myeloid-derived suppressive cell (CD11b
+
Gr-1
+
) renal infiltration (
P
<0.01) and greater frequency of myeloid and renal cells expressing the proinflammatory marker CD36 (
P
<0.05). Atrasentan reversed or reduced all of the above changes (
P
<0.05) except the endothelial dysfunction and collagen expression and reduced renal artery flow. These results demonstrate that long-term exposure to endothelial human ET-1 overexpression causes sustained blood pressure elevation and vascular and renal injury via ET
A
receptors.
First record of the non-indigenous isopods Paracerceis sculpta (Holmes, 1904) and Sphaeroma walkeri Stebbing, 1905 (Isopoda, Sphaeromatidae) for Madeira Island
Authors: Ramalhosa Patrício , Nebra Alfonso , Gestoso Ignacio , Canning-Clode João
Published: November 2017

While exploring the presence of non-indigenous fouling species colonizing settlement plates deployed in local marinas in Madeira Island (north-eastern Atlantic Ocean), two non-indigenous species (NIS) of free-swimming crustaceans, Paracerceis sculpta (Holmes, 1904) and Sphaeroma walkeri Stebbing, 1905 (Isopoda: Sphaeromatidae), were detected. Paracerceis sculpta is native to the Pacific Coast of North and Central America and has been introduced into many other regions worldwide. Sphaeroma walkeri is native to the northern Indian Ocean and nowadays is considered one of the most widely ship-transported species globally. Both species were collected in the marina of Funchal, Madeira Island, Portugal, during monitoring surveys in 2015. Moreover, several specimens of S. walkeri were also found in a foreign recreational yacht hull, during a dry dock inspection. These findings suggest that hull fouling is a significant vector for the introductions of marine invertebrates into the Madeira island system.
A new species of Aponogeton (Aponogetonaceae) from India with critical notes on embryo morphology
Authors: YADAV SHRIRANG RAMCHANDRA
Published: November 2017

Aponogeton wolfgangianus is described from Panamaram village in Wayanad district of Kerala, India. The morphology of the embryo, its significance in delimiting species and interspecific relationships have been discussed. Embryo morphology is species specific in Aponogeton and is of diagnostic value.
A new species of the genus Ceratagallia (Cicadellidae: Megophthalminae) from Central Mexico
Authors: PINEDO-ESCATEL J. A. , DIETRICH C. H.
Published: November 2017

Ceratagallia (Ceratagallia) brailovskyi sp. nov., is here described and illustrated from Central Mexico. The new species appears to be closely related to the C. bigeloviae species group, which includes previously described Mexican species. A key, species list, and distributional map for Ceratagallia in Mexico are provided.
Correlation of Leukocyte and Coronary Lesion Severity of Acute Myocardial Infarction
Authors: Liang Yunting , Chen Hui , Wang Ping
Published: November 2017

Leukocytes play a pivotal role in the onset and progression of acute myocardial infarction (AMI). We evaluated the relationship between leukocyte count and coronary lesion severity of AMI. We carried out a retrospective study involving 815 patients with AMI undergoing primary percutaneous coronary intervention from 2005 to 2014 at a cardiovascular center. We recorded their risk factors, routine blood parameters, and cardiovascular events during hospitalization. When thrombus and nonthrombus burden groups were compared, leukocyte count (9.55 [7.80, 12.29] vs 10.70 [8.67, 13.04]×109/L, P = .005), neutrophil count (7.48 [5.65, 10.18] vs 8.61 [6.61, 10.80]×109/L, P = .001), and neutrophil–lymphocyte ratio (NLR; 4.99 [2.97, 7.16] vs 10.70 [8.67, 13.04], P = .003) were significantly different. Patients in the total occlusion group showed higher leukocyte count, neutrophil count, and NLR compared to the nontotal occlusion group. After multivariate logistic analysis, a neutrophil count ≥8.355 × 109/L was independently associated with high thrombus burden and total coronary occlusion. Leukocyte count, neutrophil count, or NLR was not significantly related to cardiovascular events during hospitalization. In conclusion, the neutrophil count might be an independent predictor of high thrombus burden and total coronary occlusion.