bluuebunny/crossref_metadata_2025 huggingface dataset:
SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation
Authors: Xi Xin , Zhang Jing , Wang Jian , Chen Yuqin , Zhang Wenmei , Zhang Xiaoping , Du Jie , Zhu Guangfa
Published: November 2019

Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1-/-mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1-/-macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment.
Attitude of Jordanian Physicians toward Biochemistry and Genetics
Authors: Alfaqih Mahmoud A. , Khader Yousef S. , Bashir Nabil , Nusair Zuhair , Nuseir Quteiba , Nusier Mohamad
Published: November 2019

Background. Several studies found that physicians develop a negative attitude toward biochemistry and genetics disciplines. Many medical schools adopt an integrated system-based curriculum supplemented with clinical correlations. Medical schools in Jordan switched to the integrated curriculum; however, studies that evaluate the attitude of physicians toward biochemistry and genetics are lacking. Objectives. This study aimed to evaluate the attitude of physicians toward biochemistry and genetics including the correlation of their curricula with clinical practice. Materials and Methods. A structured questionnaire consisting of 40 statements was distributed to a random sample of 616 physicians practicing in private and governmental hospitals in Jordan. Participants earned their MD or MBBS degree from Jordan or other countries and were interns, residents, or specialists. Results. More than half of the participants admitted that biochemistry and genetics are intellectually challenging and were among their least favourite subjects (59.1%); however, many of them were familiar with some of the contemporary advances in biochemistry and genetics and their translational potential (64.0%). Most of the participants felt that modifying the medical school curriculum by integrating biochemical and genetic concepts with clinical teaching will motivate the medical students (74%). In univariate analysis, residents showed the most positive attitudes and were the most knowledgeable about the biochemical changes associated with diseases and about the contemporary advances in biochemistry or genetics (P<0.05). In multivariate analysis, physicians practicing in the private sector or those with more than five years of experience generally had a more positive attitude toward biochemistry and genetics (P<0.05). Conclusion. Physicians in Jordan showed an overall positive attitude toward biochemistry and genetics. This was more evident among residents, physicians with more than five years of experience, or those practicing in the private sector.
Preparation and Properties of Thermoresponsive P(N-Isopropylacrylamide-co-butylacrylate) Hydrogel Materials for Smart Windows
Authors: Park Jae-Hyung , Jang Ji-Won , Sim Jae-Hak , Kim Il-Jin , Lee Dong-Jin , Lee Young-Hee , Park Sang-Hui , Kim Han-Do
Published: November 2019

Thermoresponsive polymers that exhibit phase transition in response to temperature change can be used as material for smart windows because they can control solar light transmission depending on the outside temperature. The development of thermoresponsive polymers for a smart window that can be used over a wide temperature range is required. Therefore, to obtain smart window materials that can be used at various temperatures, three-dimensional thermoresponsive P(NIPAm-co-BA) hydrogels were prepared by free radical polymerization from main monomer N-isopropylacrylamide, comonomer butyl acrylate, and crosslinking agent N,N′-methylenebisacrylamide (MBAm) in this study. This study examined the effect of BA content on the lower critical solution temperature (LCST) and the solar light transmittance of crosslinked P(NIPAm-co-BA) hydrogel films. The LCST of hydrogel films was found to be significantly decreased from 34.3 to 29.5°C with increasing BA content from 0 to 20 mol%. It was found that the transparent films at T=25°C (TLCST). These results suggested that the crosslinked P(NIPAm-co-BA) hydrogel materials prepared in this study could have high potential for application in smart window materials.
A Novel Space Large Deployable Paraboloid Structure with Power and Communication Integration
Authors: Zheng Tao , Fei Zheng , Rui Xi , Yan Lide
Published: November 2019

The combination of a solar array and a communication antenna can reduce the entire mass, physical size, and cost in space applications. Currently, related studies mainly focus on the combination of the two structures on the one flat plate structure (FPS). Compared with the FPS, a paraboloid structure has a lower surface density and higher conversion efficiency. Therefore, a novel space large deployable paraboloid structure with power and communication integration (SSPCI) is proposed and designed in detail, for spacecraft on a sun synchronous earth orbit; it consists of a cable mesh membrane reflector (CMMR), an energy conversion device (ECD), and a three-extensible-rod (TER) pointing mechanism. To achieve the goal of integrating power and communication, the TER pointing mechanism drives the CMMR/ECD to track the sun in the sunshine region or to turn to face the ground station/other target in the Earth’s shadow region. Then, through simulation analyses of the deploying process, static force at a limit orientation, and sun tracking process of the SSPCI, it is proved that the SSPCI is feasible and has satisfactory performance. Finally, deploying experiments of the folded hoop of the CMMR and sun tracking experiments of the TER pointing mechanism on the ground were carried out successfully, which proves that the folded hoop can be deployed successfully with fairly high deploying dependability, and the TER pointing mechanism is feasible for the SSPCI from the mechanism principle and the control mode in space applications indirectly. Moreover, the tracking accuracy of the TER pointing mechanism is estimated to be within ±0.4° although the machining precision of its components is not high.
The Role of Cathepsin B in Peritoneal Fibrosis due to Peritoneal Dialysis
Authors: Sung Su Ah , Kim Dong Hee , Oh Kook-Hwan , Han Sang Youb , Han Kum Hyun
Published: November 2019

Glucose-containing peritoneal dialysis (PD) solution causes peritoneal fibrosis (PF) characterized by accumulation of extracellular matrix (ECM) in the submesothelial layer. Cathepsin B is a lysosomal cysteine protease that degrades ECM, but its role in the PF remains unclear. Thus, we investigated the role of cathepsin B in PF. Procathepsin B was measured in the 73 PD effluents of 68 patients. Procathepsin B and cathepsin B after exposure of glucose and the effects of cathepsin B on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and urokinase-type plasminogen activator (uPA) were measured in the supernatant of cultured human peritoneal mesothelial cells (HPMCs). The effect of cathepsin B and its inhibitor, cystatin C, on PF was investigated in the murine model. Procathepsin B was measured at 3.6 μg/L in serum and 5.4 μg/L in PD effluent and positively correlated to the cancer antigen (CA) 125. The treatment with 4.25% glucose increased procathepsin B by 3.1-fold and cathepsin B by 5.9-fold in the HPMCs. Cathepsin B induced the secretion of MMP-1, -2, and -3 and TIMP-1 in the HPMCs, but uPA was not excreted. In the PF murine models, cathepsin B reduced the thickness of the submesothelial layer and cystatin C attenuated the effect of cathepsin B. HPMCs secrete cathepsin B with exposure of PD solution, and cathepsin B might help protect against PF.
Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers
Authors: Mamidi Tarun Karthik Kumar , Wu Jiande , Hicks Chindo
Published: November 2019

Background. A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods. We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results. We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion. The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.
The Nrf2/HO-1 Axis as Targets for Flavanones: Neuroprotection by Pinocembrin, Naringenin, and Eriodictyol
Authors: Habtemariam Solomon
Published: November 2019

Flavanones are a group of flavonoids that derive from their immediate chalcone precursors through the action of chalcone isomerase enzymes. The Aromatic A and B rings, C4-keto group, and the 15-carbon flavonoid skeleton are all evident in flavanones, but a notable absence of C2-C3 double bond and a lack of oxygenation at C-3 position of the C-ring makes them distinctively different from other groups such as flavonols (e.g., quercetin). On the basis of oxygenation level in the B ring, flavanones can vary from each other as exemplified by pinocembrin (no oxygenation), naringenin (4′-hydroxyl), or eriodictyol (3′,4′-dihydroxyl substitution). These groups are generally weaker free radical scavengers as compared to quercetin and derivatives though eriodictyol has a better free radical scavenging profile within the group due to the presence of the catechol functional moiety. In this communication, their antioxidant potential through the induction of antioxidant defenses is scrutinized. These compounds as exemplified by pinocembrin could induce the nuclear factor erythroid 2-related factor 2- (Nrf2-) heme oxygenase-1 (HO-1) axis leading to amelioration of oxidative stress in cellular and animal models. Their neuroprotective effect through such mechanism is discussed.
Increased Serum Angiotensin II Is a Risk Factor of Nonalcoholic Fatty Liver Disease: A Prospective Pilot Study
Authors: Li Yue , Xiong Feng , Xu Wen , Liu Side
Published: November 2019

Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. In this prospective study, we aim to explore the role of angiotensin II (Ang II) and NLRP3 inflammasome in NAFLD patients. Methods. We prospectively enrolled 96 patients in our hospital from September 2014 to February 2016. Patients were divided into two groups (NAFLD group and Control group), and the serum Ang II level, IL-1β, IL-18, and lipids were analyzed. Correlation and multivariable analyses were used in order to identify the potential risk factors of NAFLD. Results. Although the two groups share a similar demographic background, the Ang II level of NAFLD group patients was significantly higher than that of the Control group (42.18±12.37 vs. 36.69±13.90, p=0.014) when abdominal ultrasound was used for grouping. This finding was confirmed when a FibroScan Cap value was selected to divide participants into the NAFLD group and Control group (41.16±13.06 vs. 34.85±12.64, p=0.040). Multivariable analysis showed that Ang II level is an independent risk factor of NAFLD whether abdominal ultrasound (OR=1.056, p=0.037) or FibroScan Cap value (OR=1.069, p=0.013) was deemed as the diagnostic standard. Furthermore, stepwise regression analysis was carried out between Ang II with other parameters and we discovered that Ang II had a linear correlation with IL-1β. Conclusion. Ang II levels of NAFLD patients significantly increased, and elevated Ang II level is an independent risk factor of NAFLD. Our preliminary results also indicate that Ang II may promote the development of NAFLD by activating NLRP3 inflammasome.
Coherent Signal Parameter Estimation by Exploiting Decomposition of Tensors
Authors: Liu Long , Wang Ling , Wang Yuexian , Xie Jian , Zhang Zhaolin
Published: November 2019

The problem of parameter estimation of coherent signals impinging on an array with vector sensors is considered from a new perspective by means of the decomposition of tensors. Signal parameters to be estimated include the direction of arrival (DOA) and the state of polarization. In this paper, mild deterministic conditions are used for canonical polyadic decomposition (CPD) of the tensor‐based signal model; i.e., the factor matrices can be recovered, as long as the matrices satisfy the requirement that at least one is full column rank. In conjoint with the estimation of signal parameters via the algebraic method, the DOAs and polarization parameters of coherent signals can be resolved by virtue of the first and second factor matrices. Hereinto, the key innovation of the proposed approach is that the proposed approach can effectively estimate the coherent signal parameters without sacrificing the array aperture. The superiority of the proposed algorithm is shown by comparing with the algorithms based on higher order singular value decomposition (HOSVD) and Toeplitz matrix. Theoretical and numerical simulations demonstrate the effectiveness of the proposed approach.
Dynamic Characteristics of Offshore Natural Gas Hydrate Dissociation by Depressurization in Marine Sediments
Authors: Liu Xinfu , Liu Chunhua , Wu Jianjun
Published: November 2019

Dynamic characteristics of offshore natural gas hydrate (NGH) dissociation will provide the theoretical basis to analyze technical issues of oceanic hydrate exploitation. A mathematical model is developed to simulate offshore NGH dissociation by depressurization in marine sediments. Different phase combination statuses are involved in the process of NGH dissociation by taking ice melting and water freezing into account. The proposed methodology can analyze the processes of hydrate and water phase transitions, decomposition kinetics and thermodynamics, viscosity and permeability, ice-water phase equilibrium, and natural gas and water production. A set of an experimental system is built and consists of one 3-D visual reactor vessel, one isothermal seawater vessel, one natural gas and water separator, and one data acquisition unit. The experiments on offshore NGH dissociation by depressurization in 3-D marine sediments are carried out, and this methodology is validated against the full-scale experimental data measured. The results show that during the prophase, natural gas flow is preceded by water flow into the production wellbore and natural gas occupies more continuous flow channels than water under a large pressure gradient. Then, the natural gas flow rate begins to decline accompanied by an increase of water production. During the second phase, natural gas flow rate decreases slowly because of the decreased temperature of hydrate-bearing formation and low pressure gradient. The lower the intrinsic permeability in marine sediments, the later the water flow rate reaches the peak production. And the space interval of the production wellbore should be enlarged by an increase of the intrinsic permeability. The stable period of natural gas production enhances, and the water flow rate reduces with the increase of bottom-hole pressure in production wellbores. The main reason is the slow offshore NGH dissociation under the low producing pressure and the restriction of heat conductivity under the low temperature.
Two Functional TP53 Genetic Variants and Predisposition to Keloid Scarring in Caucasians
Authors: Dmytrzak Andrzej , Boroń Agnieszka , Łoniewska Beata , Lewandowska Klaudyna , Gorący Iwona , Kaczmarczyk Mariusz , Ciechanowicz Andrzej
Published: November 2019

Introduction. Keloid is defined as a benign proliferative scar that grows beyond the confines of the original insult to the skin, invading into adjacent normal tissue. The pathogenesis of keloid is complex, and many evidences suggest the influence of genetic factors, among them the polymorphisms of the TP53 gene encoding tumor protein p53. Objective. To investigate the association of rs1042522 (c.215G>C, p.Arg72Pro) and rs17878362 (16-bp insertion/duplication in intron 3) variants, two most frequently analyzed TP53 functional polymorphisms and the risk of keloid in Polish patients. Materials and Methods. The rs1042522 and rs17878362 polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes of 86 keloid patients and from cordial blood leukocytes of 100 newborn infants consisting control group. Results. The rs1042522 and rs17878362 TP53 genotype distributions both in keloid patients and in the control group conformed to the expected Hardy–Weinberg equilibrium. No significant differences in the distribution of rs1042522 and rs17878362 TP53 alleles or genotypes have been found between keloid patients and newborn controls. There is tight, but not complete, linkage disequilibrium between rs1042522 and rs17878362 TP53 polymorphisms (D′ = 0.667, r = 0.448, and p=0). No significant differences in the distribution of rs1042522 and rs17878362 TP53 haplotypes or diplotypes have been found between keloid patients and newborn controls. Conclusions. Our results suggest the lack of association of rs1042522 and rs17878362 TP53 polymorphisms and their haplotypes or diplotypes with the susceptibility to keloid scarring in Polish patients.
Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study
Authors: Mahmoudi Michael , Gormaz Juan Guillermo , Erazo Marcia , Howard Michael , Baeza Cristian , Feelisch Martin , Curzen Nick , Olechowski Bartosz , Fernandez Bernadette , Minnion Magdalena , Mikus-Lelinska Monika , Meiss Mia , Lau Laurie , Valls Nicolas , Gajardo Abraham I. J. , Rivotta Amy , Carrasco Rodrigo , Cavada Gabriel , Vergara Maria Jesus , Maluenda Gabriel
Published: November 2019

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3±9.5 vs. 74.2±4.1 years; P<0.01) and had a higher mean STS risk score (6.6±4.8 vs. 3.2±3.0; P<0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.
Malaria Prevention Measures among Pregnant Women: A Population-Based Survey in Nnewi, Nigeria
Authors: Bhalla Devender , Cleenewerck Laurent , Okorafor Kalu Stephen , Abubakar Gulma Kabiru
Published: November 2019

We examined factors related to the uptake of two malaria prevention measures, insecticide-treated bed-nets and prophylactic sulphadoxine-pyrimethamine (SP), among pregnant women in Nnewi, Nigeria. The survey had a quantitative and qualitative part. For each part, the subjects meeting our inclusion criteria were systematically identified in a population-based manner. For the qualitative part, focused group discussions, in-depth interviews with a wide variety of stakeholders (e.g., health workers, males whose wives are pregnant, and drug and net sellers), and key informants including doctors and nurses were held. All data covered various aspects related to the topics. A total of 384 subjects participated. The mean age was 28.9 years (95% CI 23.4–34.5). The primigravidae (odds 1.8–2.3) and illiterates (odds 4.1–13.5) were less likely to sleep under the net. Primigravidae were 2.0x less likely to uptake adequate SP. The uptake was also associated with having adequate knowledge on SP (2.4x), completing usual (≥4 visits) antenatal visits (3.9x), and being in the best (≥9 visits) antenatal visit scenario (10.5x). Other barriers identified were thermal discomfort, lack of availability, cost, and unsupervised uptake of SP. Based on a representative sample, systematic procedures, and within current evaluation limits, we conclude that primigravidae and those with no formal education and inadequate antenatal visits should be the foremost group for encouraging uptake of malaria prevention measures. The policymakers should resolve issues of thermal discomfort, availability, cost, unsupervised uptake, and inadequate awareness and confidence on SP prophylaxis. The solutions are available and should be actively sought.
Effectiveness of Dose Adjustment of Insulin in Type 2 Diabetes among Hemodialysis Patients with End-Stage Renal Disease: A Randomized Crossover Study
Authors: Singhsakul Amol , Supasyndh Ouppatham , Satirapoj Bancha
Published: November 2019

Determining insulin requirements for hemodialysis patients with end-stage renal disease (ESRD) is difficult. We performed a randomized crossover study among type 2 diabetes (T2DM) patients with ESRD on continuous hemodialysis and receiving standard insulin for glycemic control. The patients were randomized in 2 groups: daily insulin needed on the day after hemodialysis and a 25% decrease in daily insulin needed on the day after hemodialysis. A total of 51 T2DM patients with ESRD were enrolled. The adjusted-insulin group had higher plasma glucose levels at the 2nd hour of dialysis than those of the nonadjusted-insulin group. Incidence of hypoglycemia per dialysis session (3.3% vs. 0.7%, P=0.02) and symptoms related to hypoglycemia (6.9% vs. 0.7%, P=0.001) were more frequent in the nonadjusted-insulin group. A reduced insulin administration of 25% among T2DM patients undergoing hemodialysis on the day of dialysis was associated with sustained glycemic efficacy and the production of fewer hypoglycemic symptoms. This trial is registered with TCTR20180724002.
Efficacy of Virtual Reality Rehabilitation after Spinal Cord Injury: A Systematic Review
Authors: de Araújo Amanda Vitória Lacerda , Neiva Jaqueline Freitas de Oliveira , Monteiro Carlos Bandeira de Mello , Magalhães Fernando Henrique
Published: November 2019

Background. Spinal cord injury (SCI) is often associated with long-term impairments related to functional limitations in the sensorimotor system. The use of virtual reality (VR) technology may lead to increased motivation and engagement, besides allowing a wide range of possible tasks/exercises to be implemented in rehabilitation programs. The present review aims to investigate the possible benefits and efficacy of VR-based rehabilitation in individuals with SCI. Methods. An electronically systematic search was performed in multiple databases (PubMed, BVS, Web of Science, Cochrane Central, and Scielo) up to May 2019. MESH terms and keywords were combined in a search strategy. Two reviewers independently selected the studies in accordance with eligibility criteria. The PEDro scale was used to score the methodological quality and risk of bias of the selected studies. Results. Twenty-five studies (including 482 participants, 47.6 ± 9.5 years, 73% male) were selected and discussed. Overall, the studies used VR devices in different rehabilitation protocols to improve motor function, driving skills, balance, aerobic function, and pain level, as well as psychological and motivational aspects. A large amount of heterogeneity was observed as to the study design, VR protocols, and outcome measures used. Only seven studies (28%) had an excellent/good quality of evidence. However, substantial evidence for significant positive effects associated with VR therapy was found in most of the studies (88%), with no adverse events (88%) being reported. Conclusion. Although the current evidence is limited, the findings suggest that VR-based rehabilitation in subjects with SCI may lead to positive effects on aerobic function, balance, pain level, and motor function recovery besides improving psychological/motivational aspects. Further high-quality studies are needed to provide a guideline to clinical practice and to draw robust conclusions about the potential benefits of VR therapy for SCI patients. Protocol details are registered on PROSPERO (registration number: CRD42016052629).
Preconcentration and Determination of Psychotropic Drugs in Urine Samples by Ion Mobility Spectrometry with Electrospray Ionization Coupling On-Line Single-Drop Liquid-Liquid-Liquid Microextraction
Authors: Li Shu
Published: November 2019

A method for analysis of psychotropic drugs in urine is investigated using a novel single-drop liquid-liquid-liquid microextraction (SDLLLME) apparatus as an electrospray emitter in ion mobility spectrometry (IMS). In this method, ketamine and pethidine are back-extracted into the acceptor phase (water and methanol) from the water and methanol immiscible organic phase. Sensitivity of extraction is improved as it does not require further methanol-adding procedure. Factors affecting the extraction of psychotropic drugs are characterized, including organic solvent type, extraction time, and concentration of NaOH/Ac in the donor/acceptor phase. The best extraction sensitivity is obtained with 600 μL dodecane as the organic phase, 30 minutes extraction time, and 10 mL donor phase with 0.01 M sodium hydroxide (NaOH) and 3 μL acceptor phase with 0.5 M acetic acid (Ac). Using this method, the two analytes can be extracted and analyzed simultaneously, showing this method is valuable for field application.
Are Feature Agreement Statistics Alone Sufficient to Validate Modelled Flood Extent Quality? A Study on Three Swedish Rivers Using Different Digital Elevation Model Resolutions
Authors: Lim Nancy Joy , Brandt Sven Anders
Published: November 2019

Hydraulic modelling is now, at increasing rates, used all over the world to provide flood risk maps for spatial planning, flood insurance, etc. This puts heavy pressure on the modellers and analysts to not only produce the maps but also information on the accuracy and uncertainty of these maps. A common means to deliver this is through performance measures or feature statistics. These look at the global agreement between the modelled flood area and the reference flood that is used. Previous studies have shown that the feature agreement statistics do not differ much between models that have been based on digital elevation models (DEMs) of different resolutions, which is somewhat surprising since most researchers agree that high‐resolution DEMs are to be preferred over poor resolution DEMs. Hence, the aim of this study was to look into how and under which conditions the different feature agreement statistics differ, in order to see when the full potential of high‐resolution DEMs can be utilised. The results show that although poor resolution DEMs might produce high feature agreement scores (around F > 0.80), they may fail to provide good flood extent estimations locally, particularly when the terrain is flat. Therefore, when high‐resolution DEMs (1 to 5 m) are used, it is important to carefully calibrate the models by the use of the roughness parameter. Furthermore, to get better estimates on the accuracy of the models, other performance measures such as distance disparities should be considered.
Bidirectional Regulation between NDRG1 and GSK3β Controls Tumor Growth and Is Targeted by Differentiation Inducing Factor-1 in Glioblastoma
Authors: Ito Hiroshi , Watari Kosuke , Shibata Tomohiro , Miyamoto Tomofumi , Murakami Yuichi , Nakahara Yukiko , Izumi Hiroto , Wakimoto Hiroaki , Kuwano Michihiko , Abe Tatsuya , Ono Mayumi
Published: November 2019

The development of potent and selective therapeutic approaches to glioblastoma (GBM), one of the most aggressive primary brain tumors, requires identification of molecular pathways that critically regulate the survival and proliferation of GBM. Previous studies have reported that deregulated expression of N-myc downstream regulated gene 1 (NDRG1) affects tumor growth and clinical outcomes of patients with various types of cancer including glioma. Here, we show that high level expression of NDRG1 in tumors significantly correlated with better prognosis of patients with GBM. Loss of NDRG1 in GBM cells upregulated GSK3β levels and promoted cell proliferation, which was reversed by selective inhibitors of GSK3β. In contrast, NDRG1 overexpression suppressed growth of GBM cells by decreasing GSK3β levels via proteasomal degradation and by suppressing AKT and S6 cell growth signaling, as well as cell-cycle signaling pathways. Conversely, GSK3β phosphorylated serine and threonine sites in the C-terminal domain of NDRG1 and limited the protein stability of NDRG1. Furthermore, treatment with differentiation inducing factor-1, a small molecule derived from Dictyostelium discoideum, enhanced NDRG1 expression, decreased GSK3β expression, and exerted marked NDRG1-dependent antitumor effects in vitro and in vivo. Taken together, this study revealed a novel molecular mechanism by which NDRG1 inhibits GBM proliferation and progression. Our study thus identifies the NDRG1/GSK3β signaling pathway as a key growth regulatory program in GBM, and suggests enhancing NDRG1 expression in GBM as a potent strategy toward the development of anti-GBM therapeutics.

Significance:

This study identifies NDRG1 as a potent and endogenous suppressor of glioblastoma cell growth, suggesting the clinical benefits of NDRG1-targeted therapeutics against glioblastoma.
CD44 Promotes PD-L1 Expression and Its Tumor-Intrinsic Function in Breast and Lung Cancers
Authors: Kong Tim , Ahn Ryuhjin , Yang Kangning , Zhu Xianbing , Fu Zheng , Morin Geneviève , Bramley Rachel , Cliffe Nikki C. , Xue Yibo , Kuasne Hellen , Li Qinghao , Jung Sungmi , Gonzalez Anne V. , Camilleri-Broet Sophie , Guiot Marie-Christine , Park Morag , Ursini-Siegel Josie , Huang Sidong
Published: November 2019

The PD-L1 (CD274) immune-checkpoint ligand is often upregulated in cancers to inhibit T cells and elicit immunosuppression. Independent of this activity, PD-L1 has recently been shown to also exert a cancer cell–intrinsic function promoting tumorigenesis. Here, we establish this tumor-intrinsic role of PD-L1 in triple-negative breast cancer (TNBC) and non–small cell lung cancer (NSCLC). Using FACS-assisted shRNA screens, we identified the cell-surface adhesion receptor CD44 as a key positive regulator of PD-L1 expression in these cancers. Mechanistically, CD44 activated PD-L1 transcription in part through its cleaved intracytoplasmic domain (ICD), which bound to a regulatory region of the PD-L1 locus containing a consensus CD44-ICD binding site. Supporting this genetic interaction, CD44 positively correlated with PD-L1 expression at the mRNA and protein levels in primary tumor samples of TNBC and NSCLC patients. These data provide a novel basis for CD44 as a critical therapeutic target to suppress PD-L1 tumor–intrinsic function.

Significance:

CD44 is a potential target to suppress PD-L1 function in TNBC. This finding has the potential to open a new area of therapy for TNBC.
A PSCA/PGRN–NF-κB–Integrin–α4 Axis Promotes Prostate Cancer Cell Adhesion to Bone Marrow Endothelium and Enhances Metastatic Potential
Authors: Zhao Zhigang , Li Ermao , Luo Lianmin , Zhao Shankun , Liu Luhao , Wang Jiamin , Kang Ran , Luo Jintai
Published: November 2019

Distant metastasis, predominantly to bone, is the leading cause of morbidity and mortality in prostate cancer. However, the mechanisms underlying prostate cancer metastases remain unknown. Prostate cancer cells exhibited discrete adhesion to bone marrow endothelial cells (BMEC), resulting in osteotropic metastasis. Prior data showed an increased metastatic propensity of prostate stem cell antigen (PSCA)–positive prostate cancer cells. The current study sought to characterize the roles of PSCA in the adhesion of prostate cancer cells to BMECs. Cell adhesion was assessed using the adhesion assay and transendothelial migration. The expression and regulation of integrins were evaluated by qRT-PCR, Western blot, promoter-luciferase activity, and chromatin immunoprecipitation (ChIP). Functionally, the potential interacting partners of PSCA in prostate cancer cells were identified by coimmunoprecipitation and mass spectrometry (MS) analysis. The association of PSCA expression with bone metastasis was further analyzed in an in vivo model and prostate cancer patients. We found that overexpression of PSCA enhanced the adhesion capability of prostate cancer cells to BMECs through upregulating integrin-α4 expression, concurrent with transcriptionally activated NF-κB. Growth factor progranulin (PGRN) was identified as a potential interacting partner of PSCA in prostate cancer cells. Functional studies showed that downregulation of PGRN and PSCA with siRNAs in prostate cancer cells significantly suppressed the integrin-α4 expression and the adhesion to BMECs in vitro, respectively, which were restorable by exogenous PGRN. Importantly, PSCA depletion significantly reduced tumors' presence in the bone of a mouse model. Furthermore, PSCA expression is elevated in prostate cancer tissue, and significantly associated with increased Gleason score, advanced stage, bone metastasis, and poor prognosis in prostate cancer patients. We conclude that PSCA/PGRN promoted the adhesion of prostate cancer cells to BMECs through NF-κB/integrin-α4 pathways, to facilitate metastases.

Implications:

The findings presented here suggest PSCA/PGRN as a potential therapeutic target for prostate cancer metastases, especially for bone metastasis.
Does the Presence of Giant Pseudopolyps in a Patient with Newly Diagnosed Inflammatory Bowel Disease Increase the Risk of Major Thrombotic Events?
Authors: Amini Afshin , Vaezi Zahra , Talebian Amirsina , Koury Elliott , Chahla Elie
Published: November 2019

Giant inflammatory polyp and thromboembolism are uncommon complications in inflammatory bowel disease (IBD) patients. Colon mucosal inflammation is possibly the main mechanism of pathogenesis for these two complications. IBD has long been associated with hypercoagulability and thromboembolism. In fact, thromboembolism has been noted in 0.7% to 7.7% of IBD patients, with the deep veins of the legs and the pulmonary veins accounting for 90% of the cases. The proposed mechanism of this hypercoagulability involves the promotion of hemostasis that results from the inflammatory process underlying the IBD, as well as the loss of proteins, including antithrombotic factors, resulting from the inflamed bowel and increased permeability of the colonic mucosa. This process may be exacerbated by the presence of giant inflammatory polyps, which are defined as polyps in the setting of IBD with dimensions greater than 1.5 cm. The presence of these polyps leads to an increase in inflamed colonic surface area, which can accelerate the rate of protein loss, leading to an increased incidence of thrombosis. Here, we report the case of a 21-year-old female with inferior vena cava and left renal vein thromboses secondary to a newly diagnosed IBD and the presence of severe giant inflammatory polyposis. These thromboses were detected incidentally in this patient after 1 week of hospitalization. She had presented with hypoalbuminemia and elevated inflammatory markers, which raised the suspicion for possible giant inflammatory polyposis as a potential risk for her major thromboembolic events. More studies are required to explore this plausible correlation further.
Uso e abuso de drogas entre universitários e a sua interface com as políticas públicas
Authors: Camargo Elisa Carneiro Pereira , Gonçalves Jamila Souza , Felipe Adriana Olimpia Barbosa , Fava Silvana Maria Coelho Leite , Zago Márcia Maria Fontão , Dázio Eliza Maria Rezende
Published: November 2019

Objetivo: analisar o significado do uso e do abuso de álcool e/ou de outras drogas entre os universitários em consonância com as políticas públicas brasileiras sobre drogas. Método: participaram 49 universitários de uma Instituição Pública de Ensino Superior da região Sudeste do Brasil. Resultados: pela Análise de Conteúdo de Bardin elaborou-se a categoria analítica: “Dissonância entre as políticas públicas e o significado do uso de drogas entre universitários”. O uso e o abuso de drogas inicia-se na adolescência; estimulado pelos familiares e amigos, e remete à felicidade e à fuga dos problemas. Conclusão: é fundamental conhecer o significado do uso e do abuso de drogas, sob a ótica do universitário para a elaboração e a implementação de políticas públicas.
Uso de substâncias psicoativas entre estudantes universitários
Authors: Santos Dominick Danielle Mendonça , Guimarães Melissa Monteiro , Bodevan Emerson Cotta , Rocha Ricardo Lopes , Pinheiro Marcos Luciano Pimenta
Published: November 2019

O objetivo do estudo foi identificar o perfil do uso de substâncias psicoativas entre estudantes dos cursos de Ciências Biológicas, Educação Física, Enfermagem, Fisioterapia, Farmácia, Odontologia e Nutrição. Trata-se de estudo transversal, quantitativo, exploratório e descritivo, com 567 estudantes. Os dados foram coletados por meio de um questionário e analisados através da estatística descritiva. Nos resultados, verificou-se que 11,6% dos estudantes nunca experimentaram substâncias psicoativas na vida. As drogas mais prevalentes entre os universitários foram o álcool (n=501), tabaco (n=161), maconha (n=115) e cocaína (n=26). Conclui-se que o consumo de substâncias psicoativas entre os estudantes é problema que deve ser enfrentado através da implantação de ações preventivas e de redução de danos.
Modelo bioecológico para el autocontrol del consumo de alcohol y calidad de vida laboral
Authors: Mendoza Alejandra Leija , Aguirre Alicia Álvarez , Zanetti Ana Carolina Guidorizzi
Published: November 2019

Objetivo: el propósito del estudio fue derivar “The Ecology of Human Development” para explicar el autocontrol del consumo de alcohol y calidad de vida laboral desde el enfoque de enfermería. Método: análisis y aplicación de la metodología la cual contempla cinco pasos principales. Resultados: construcción del modelo Bioecológico para el autocontrol del consumo de alcohol y calidad de vida en el área laboral. Conclusiones: el desarrollo del modelo puede favorecer identificar y generar campos de acción que sean útiles en la práctica del enfermero con fundamento científico para prevenir o disminuir el consumo de alcohol en el área laboral.
Alterações mentais em trabalhadores de unidades de terapia intensiva
Authors: Silva Andressa Fernanda , Robazzi Maria Lúcia do Carmo Cruz
Published: November 2019

Objetivo: investigar as evidências científicas sobre alterações mentais em trabalhadores de Unidades de Terapia Intensiva (UTI). Método: revisão integrativa cuja busca aconteceu nas bases de dados EMBASE, MEDLINE e SCOPUS e nas bibliotecas virtuais/coleções BVS e SCIENCE DIRECT. De 141 artigos primários identificados, 33 (23,4%) atenderam aos critérios de inclusão e foram publicados em 29 periódicos de várias áreas de conhecimento. Resultados: as alterações mentais identificadas foram: estresse, sofrimento e tensão no trabalho, depressão, astenia, fadiga, sobrecarga mental e Burnout. No trabalho, também acontecemconflitos, violência e maus tratos e os trabalhadores das UTI apresentaram predisposição ao uso de psicotrópicos. Conclusão: o tema é relevante pois há um rol de alterações mentais dos trabalhadores de UTI que podem levá-los aos absenteísmos.
O uso de bebida alcoólica entre gestantes adolescentes
Authors: Cândido Tarcila Cristina Rodrigues , Ferreira Gabriela Coutinho , Moreira Denis Da Silva , Sousa Bárbara De Oliveira Prado , Cordeiro Samara Macedo , Alfredo Evellin Ribeiro , Felipe Adriana Olimpia Barbosa
Published: November 2019

Objetivo: identificar o consumo de bebida alcoólica entre as adolescentes gestantes. Método: estudo de abordagem quantitativa, descritiva e de corte transversal. Os participantes foram 27 adolescentes gestantes adscritas nas Estratégia de Saúde da Família. Resultados: constatou-se que 54% referiram fazer uso de bebida alcoólica nos últimos 12 meses e 7,4% apresentavam chance de ter diagnóstico de dependência alcoólica. Das 5 participantes que relataram ser a segunda gestação, 80% afirmaram ter utilizado álcool na gravidez anterior. Identificou-se que em relação de risco sobre o padrão de consumo de álcool 81,4% se enquadram na zona I, 14,8% na zona II e 7,4% na zona IV. Conclusão: reafirma-se a necessidade de ações de prevenção do uso de álcool na gestação e a relevância do papel do enfermeiro no acompanhamento integral durante o pré-natal.
Sex‐Specific Differences in Survival and Heart Failure Hospitalization After Cardiac Resynchronization Therapy With or Without Defibrillation
Authors: Leyva Francisco , Qiu Tian , Zegard Abbasin , McNulty David , Evison Felicity , Ray Daniel , Gasparini Maurizio
Published: November 2019

Background

Women are underrepresented in cardiac resynchronization therapy (
CRT
) trials. Some studies suggest that women fare better than men after
CRT
. We sought to explore clinical outcomes in women and men undergoing
CRT
‐defibrillation or CRT‐pacing in real‐world clinical practice.

Methods and Results

A national database (Hospital Episode Statistics for England) was used to quantify clinical outcomes in 43 730 patients (women: 10 890 [24.9%]; men: 32 840 [75.1%]) undergoing
CRT
over 7.6 years, (median follow‐up 2.2 years, interquartile range, 1–4 years). In analysis of the total population, the primary end point of total mortality (adjusted hazard ratio [
aHR
], 0.73; 95% CI, 0.69–0.76) and the secondary end point of total mortality or heart failure hospitalization (
aHR
, 0.79, 95% CI 0.75–0.82) were lower in women, independent of known confounders. Total mortality (
aHR
, 0.73; 95% CI, 0.70–0.76) and total mortality or heart failure hospitalization (
aHR
, 0.79; 95% CI, 0.75–0.82) were lower for
CRT
‐defibrillation than for
CRT
‐pacing. In analyses of patients with (
aHR
, 0.89; 95% CI, 0.80–0.98) or without (
aHR
, 0.70; 95% CI, 0.66–0.73) a myocardial infarction, women had a lower total mortality. In sex‐specific analyses, total mortality was lower after
CRT
‐defibrillation in women (
aHR
, 0.83;
P
=0.013) and men (
aHR
, 0.69;
P
<0.001).

Conclusions

Compared with men, women lived longer and were less likely to be hospitalized for heart failure after
CRT
. In both sexes,
CRT
‐defibrillation was superior to
CRT
‐pacing with respect to survival and heart failure hospitalization. The longest survival after
CRT
was observed in women without a history of myocardial infarction.
Outcomes of Multi‐Organ Transplant in Adult Patients With Congenital Heart Disease
Authors: Wong Kristen , Tecson Kristen , Cedars Ari
Published: November 2019

Background

The prevalence of adult congenital heart disease (
ACHD
) is increasing in the United States because of improved survival into adulthood. The unique physiology of ACHD commonly leads to multiorgan dysfunction, prompting interest in outcomes after multiorgan (heart+X) transplantation.

Methods and Results

We queried the SRTR (Scientific Registry of Transplant Recipients) database to examine 5‐year outcomes in
ACHD
patients (aged ≥18 years) who underwent dual organ (heart+kidney/liver/lung) transplantation between 2000 and 2016. Cox proportional hazards models were constructed to look at survival of dual organ transplant recipients versus heart‐only recipients in the
ACHD
population and heart+lung recipients versus heart‐only recipients in the
ACHD
populations and versus non‐
ACHD
recipients of heart+lung transplant. We then constructed a multivariable model to investigate independent risk factors for 5‐year mortality after multiorgan transplant. Overall, 5‐year mortality was greater for multiorgan (heart+kidney/liver/lung) transplant compared with heart‐only transplant. On further analysis, only heart+lung transplant was associated with increased mortality. Outcomes after heart+lung transplant were no different between the
ACHD
and non‐
ACHD
population. Risk factors for increased risk of 5‐year mortality in
ACHD
patients after multiorgan transplant included heart+lung transplant, previous cardiac surgery, and severe functional limitation.

Conclusions

The mortality risk associated with multiorgan heart transplant in
ACHD
patients is attributable primarily to heart+lung transplants. Multiorgan transplant in
ACHD
does not convey increased risk compared with the non‐
ACHD
population. Need for multiorgan transplant should not be an impediment to listing
ACHD
patients needing a heart transplant.