bluuebunny/crossref_metadata_2025 huggingface dataset:
APOL1 and Kidney Disease: From Genetics to Biology
Authors: Friedman David J. , Pollak Martin R.
Published: November 2019

Genetic variants in the APOL1 gene, found only in individuals of recent African ancestry, greatly increase risk of multiple types of kidney disease. These APOL1 kidney risk alleles are a rare example of genetic variants that are common but also have a powerful effect on disease susceptibility. These alleles rose to high frequency in sub-Saharan Africa because they conferred protection against pathogenic trypanosomes that cause African sleeping sickness. We consider the genetic evidence supporting the association between APOL1 and kidney disease across the range of clinical phenotypes in the APOL1 nephropathy spectrum. We then explore the origins of the APOL1 risk variants and evolutionary struggle between humans and trypanosomes at both the molecular and population genetic level. Finally, we survey the rapidly growing literature investigating APOL1 biology as elucidated from experiments in cell-based systems, cell-free systems, mouse and lower organism models of disease, and through illuminating natural experiments in humans.
CD8+ T cells regulate liver injury in obesity-related nonalcoholic fatty liver disease
Authors: Breuer Denitra A. , Pacheco Maria Cristina , Washington M. Kay , Montgomery Stephanie A. , Hasty Alyssa H. , Kennedy Arion J.
Published: November 2019

Nonalcoholic steatohepatitis (NASH) has increased in Western countries due to the prevalence of obesity. Current interests are aimed at identifying the type and function of immune cells that infiltrate the liver and key factors responsible for mediating their recruitment and activation in NASH. We investigated the function and phenotype of CD8+ T cells under obese and nonobese NASH conditions. We found an elevation in CD8 staining in livers from obese human subjects with NASH and cirrhosis that positively correlated with α-smooth muscle actin, a marker of hepatic stellate cell (HSC) activation. CD8+ T cells were elevated 3.5-fold in the livers of obese and hyperlipidemic NASH mice compared with obese hepatic steatosis mice. Isolated hepatic CD8+ T cells from these mice expressed a cytotoxic IL-10-expressing phenotype, and depletion of CD8+ T cells led to significant reductions in hepatic inflammation, HSC activation, and macrophage accumulation. Furthermore, hepatic CD8+ T cells from obese and hyperlipidemic NASH mice activated HSCs in vitro and in vivo. Interestingly, in the lean NASH mouse model, depletion and knockdown of CD8+ T cells did not impact liver inflammation or HSC activation. We demonstrated that under obese/hyperlipidemia conditions, CD8+ T cell are key regulators of the progression of NASH, while under nonobese conditions they play a minimal role in driving the disease. Thus, therapies targeting CD8+ T cells may be a novel approach for treatment of obesity-associated NASH.

NEW & NOTEWORTHY Our study demonstrates that CD8+ T cells are the primary hepatic T cell population, are elevated in obese models of NASH, and directly activate hepatic stellate cells. In contrast, we find CD8+ T cells from lean NASH models do not regulate NASH-associated inflammation or stellate cell activation. Thus, for the first time to our knowledge, we demonstrate that hepatic CD8+ T cells are key players in obesity-associated NASH.
A new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B
Authors: Yanda Murali K. , Guggino William B. , Cebotaru Liudmila
Published: November 2019

Clostridium difficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. Its virulence derives from two toxins, toxin CD, A and B (TcdA and TcdB) (Borriello et al. Rev Infect Dis 12, Suppl 2: S185-191, 1990). Among the prime candidates for CD colonization are patients with cystic fibrosis (CF), who are routinely treated with antibiotics and frequently hospitalized. Indeed, ~50% of patients with CF are colonized with virulent forms of CD but do not exhibit diarrhea (Bauer et al. Clin Microbiol Infect 20: O446–O449, 2014; Binkovitz et al. Am J Roentgenol 172: 517–521, 199; Zemljic et al. Anaerobe 16: 527–532, 2010). We found that TcdB has global effects on colonic cells, including reducing the steady-state levels of sodium-proton exchange regulatory factors, reducing the levels of heat shock protein (Hsp) 27, and increasing the fraction of total Hsp27 bound to the cystic fibrosis transmembrane conductance regulator (CFTR). Also, since some mutations in CFTR seem to be protective, we asked whether CFTR is a target of TcdB. We show here that TcdB increases the maturation of CFTR and transiently increases its function. These combined effects promote increased surface expression of CFTR, resulting in a transient increase in Cl− secretion. This increase is followed by a precipitous decline in both CFTR-dependent Cl− secretion and transepithelial resistance (TER), suggesting a breakdown in the epithelial cells’ tight junctions. We also found that overexpressing Hsp27 reverses some of the deleterious effects of TcdB, in particular preserving TER and therefore likely the maintenance of barrier function. Thus, our data suggest that Hsp27 plays a role in the diarrhea generated by CD infection and is a potential therapeutic target for treating this diarrhea.

NEW & NOTEWORTHY Clostridium difficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. We provide new evidence that heat shock protein (Hsp) 27 is one of the key players in CD pathology and that increasing Hsp27 can prevent the decrease in transepithelial resistance induced by toxin CD B, pointing the way for pharmacologic therapies for patients with chronic CD infection that can increase Hsp27 as a means to mitigate the effects of CD on gastrointestinal pathology.
Targeting glycolysis in proliferative kidney diseases
Authors: Ghazi Susan , Polesel Marcello , Hall Andrew M.
Published: November 2019

Glycolytic activity is increased in proliferating cells, leading to the concept that glycolysis could be a therapeutic target in cystic diseases and kidney cancer. Preclinical studies using the glucose analog 2-deoxy-d-glucose have shown promise; however, inhibiting glycolysis in humans is unlikely to be without risks. While proximal tubules are predominantly aerobic, later segments are more glycolytic. Understanding exactly where and why glycolysis is important in the physiology of the distal nephron is thus crucial in predicting potential adverse effects of glycolysis inhibitors. Live imaging techniques could play an important role in the process of characterizing cellular metabolism in the functioning kidney. The goal of this review is to briefly summarize recent findings on targeting glycolysis in proliferative kidney diseases and to highlight the necessity for future research focusing on glycolysis in the healthy kidney.
Distinct Redox Signalling following Macrophage Activation Influences Profibrotic Activity
Authors: Lewis Caitlin V. , Vinh Antony , Diep Henry , Samuel Chrishan S. , Drummond Grant R. , Kemp-Harper Barbara K.
Published: November 2019

Aims. To date, the ROS-generating capacities of macrophages in different activation states have not been thoroughly compared. This study is aimed at determining the nature and levels of ROS generated following stimulation with common activators of M1 and M2 macrophages and investigating the potential for this to impact fibrosis.Results. Human primary and THP-1 macrophages were treated with IFN-γ+LPS or IL-4-activating stimuli, and mRNA expression of established M1 (CXCL11, CCR7, IL-1β) and M2 (MRC-1, CCL18, CCL22) markers was used to confirm activation. Superoxide generation was assessed by L-012-enhanced chemiluminescence and was increased in both M(IFN-γ+LPS) and M(IL-4) macrophages, as compared to unpolarised macrophages (MΦ). This signal was attenuated with NOX2 siRNA. Increased expression of the p47phox and p67phox subunits of the NOX2 oxidase complex was evident in M(IFN-γ+LPS) and M(IL-4) macrophages, respectively. Amplex Red and DCF fluorescence assays detected increased hydrogen peroxide generation following stimulation with IL-4, but not IFN-γ+LPS. Coculture with human aortic adventitial fibroblasts revealed that M(IL-4), but not M(IFN-γ+LPS), enhanced fibroblast collagen 1 protein expression. Macrophage pretreatment with the hydrogen peroxide scavenger, PEG-catalase, attenuated this effect.Conclusion. We show that superoxide generation is not only enhanced with stimuli associated with M1 macrophage activation but also with the M2 stimulus IL-4. Macrophages activated with IL-4 also exhibited enhanced hydrogen peroxide generation which in turn increased aortic fibroblast collagen production. Thus, M2 macrophage-derived ROS is identified as a potentially important contributor to aortic fibrosis.
Analysis of College Students’ Public Opinion Based on Machine Learning and Evolutionary Algorithm
Authors: Zhang Jinqing , Zhang Pengchao , Xu Bin
Published: November 2019

The recent information explosion may have many negative impacts on college students, such as distraction from learning and addiction to meaningless and fake news. To avoid these phenomena, it is necessary to verify the students’ state of mind and give them appropriate guidance. However, many peculiarities, including subject focused, multiaspect, and low consistency on different samples’ interests, bring great challenges while leveraging the mainstream opinion mining method. To solve this problem, this paper proposes a new way by using a questionnaire which covers most aspects of a student’s life to collect comprehensive information and feed the information into a neural network. With reliable prediction on students’ state of mind and awareness of feature importance, colleges can give students guidance associated with their own experience and make macroscopic policies more effective. A pipeline is proposed to relieve overfitting during the collected information training. First, the singular value decomposition is used in pretreatment of data set which includes outlier detection and dimension reduction. Then, the genetic algorithm is introduced in the training process to find the proper initial parameters of network, and in this way, it can prevent the network from falling into the local minimum. A method of calculating the importance of students’ features is also proposed. The experiment result shows that the new pipeline works well, and the predictor has high accuracy on predicting fresh samples. The design procedure and the prediction design will provide suggestions to deal with students’ state of mind and the college’s public opinion.
Sliding Dynamics of a Filippov Forest‐Pest Model with Threshold Policy Control
Authors: Liu Lirong , Xiang Changcheng , Tang Guangyao , Fu Yuan
Published: November 2019

A novel Filippov forest‐pest system with threshold policy control (TPC) is established while an economic threshold (ET) is used to guide switching. The aim of our work is to address how to reasonably and successfully control pests by means of sliding dynamics for the Filippov system. On the basis of the above considerations, conditions for the existence and stability of equilibria of subsystems are addressed, and the sliding segments and several types of equilibria of the proposed system are defined. These equilibria include the regular/virtual equilibrium, pseudoequilibrium, boundary equilibrium, and tangent point. Further, not only are the relations between nullclines and equilibria of the Filippov system discussed, but the relations between pseudoequilibrium, nullclines, and the sliding segment are discussed. More importantly, four cases of sliding bifurcations of the Filippov system with respect to different types of equilibria of subsystems are investigated, and the corresponding biological implications concerning integrated pest management (IPM) are analyzed. Our results show that the points of intersection between nullclines are equilibria of the system, and the two endpoints of the sliding segment are on the nullclines. It is also verified that the pseudoequilibrium is the point of intersection of the sliding segment and nullclines of the Filippov system, and the pseudoequilibrium exists on the sliding segment. More interestingly, sliding dynamics analysis reveals that the Filippov system has sliding limit cycles, a bistable state and a stable refuge equilibrium point, and the optimal time and strategy for controlling pests are provided.
Effects of Polygonatum sibiricum Polysaccharides (PSP) on Human Esophageal Squamous Cell Carcinoma (ESCC) via NF-κB Signaling Pathway
Authors: Zhou Weizheng , Hong Jiang , Zhu Ji , Wang Xiaowei
Published: November 2019

Objective. To explore the effects of different concentrations of Polygonatum sibiricum polysaccharides (PSP) on human esophageal squamous cell carcinoma (ESCC) cell line Eca109 and explore the new approach for the treatment of ESCC. Methods. Eca109 cells were divided into 5 groups, including one control group and 4 experimental groups where the concentrations of PSP used were 50, 100, 200, and 400 μg/mL. The proliferation rate of Eca109 cells in each group was measured with the CCK8 assay, and the apoptosis rate in each group was analyzed by flow cytometry; the in vitro scratch assay was used to determine the migration ability of Eca109 cells after PSP treatment; the expression levels of IL-1, IL-6, IL-10, TNF-α, and TGF-β were measured by RT-PCR, and the expression levels of TLR4 and proteins that are related to NF-κB signaling pathways were determined by Western blot. Results. PSP significantly inhibited the proliferation of Eca109 cells (p<0.05) on a time- and dose-dependent manner; the apoptosis rates of Eca109 cells in experimental groups were significantly increased after 48 h of culture (p<0.05); PSP significantly reduced the migration and invasion ability of Eca109 cells (p<0.05); RT-PCR results showed that the expression of IL-10 in Eca109 cells increased significantly after treatment with PSP (p<0.05), while the expression of IL-1, IL-6, TNF-α, and TGF-β decreased significantly (p<0.05). Compared with the control group, the expression level of TLR4, NF-κB/p50, and NF-κB/p65 protein in each experimental group was significantly lower than that in the control group (p<0.05). Conclusions. PSP significantly inhibited the proliferation, invasion, and migration of Eca109 cells and promoted cell apoptosis. These observed effects were probably due to the PSP’s inhibition on the NF-κB signaling pathway in Eca109 cells via the regulation of the TLR4 expression.
The Critical Adiabatic Linear Tapered Waveguide Combined with a Multimode Waveguide Coupler on an SOI Chip
Authors: Chiu C. L. , Liao Yen-Hsun
Published: November 2019

A multimode waveguide interference (MMI) coupler is combined with a critical linear tapered waveguide on a silicon-on-insulator (SOI) chip. When the TE0 mode is a critical adiabatic mode conversion from a single-mode waveguide to an extreme linear tapered waveguide combined with an MMI, this linear tapered waveguide is achieved to the maximum divergence angle (i.e., the shortest length). The maximum divergence angle is expressed by θ ≤ 2 tan−1[(0.35Wmmi − Ws)/(0.172Lmmi)] under a 1 × 1 MMI combined with this critical linear tapered waveguide. The expression formula is demonstrated by three different widths of a 1 × 1 MMI of 4 μm/8 μm/12 μm combined with the critical linear tapered waveguide. So, the maximum divergence angle is obtained at θ = 16°/14°/8°, with respect to this linear tapered waveguide loss of 0.022 dB/0.172 dB/0.158 dB, and this linear tapper length is reduced by 93.7%/92.9%/87.5% than the divergence angle θ = 1°. The output power of a 1 × 1 MMI combined with a critical linear tapered waveguide is enhanced at least 1.5 times under 0.95 above condition.
Micro-CT Characterization of Wellbore Cement Degradation in SO42-–Bearing Brine under Geological CO2 Storage Environment
Authors: Gan Manguang , Zhang Liwei , Miao Xiuxiu , Wang Yan , Fu Xiaojuan , Bai Mingxing , Li Xiaochun
Published: November 2019

In order to explore the process of acid- and CO2-induced degradation of wellbore cement and the development of pre-existing leakage channels in wellbore cement under sulfate-rich geological CO2 storage conditions, wellbore cement samples were immersed in SO42--bearing brine solution for 7 days, and the samples after reacting with the low and circumneutral pH solutions were scanned by a micro-CT scanner. HCl+Na2SO4 solution was used to simulate the low-pH condition in deep formation waters and the possible existence of high sulfate ion content in deep formation waters. The acidification and carbonation results were compared, and the results given different pH values and different curing conditions were compared as well. The results show that the degradation of cement was related to the pH value of the reaction solution. There was a significant dissolution in the exterior of the cement sample after exposure to the low-pH solution, but the dissolution surrounding a penetrating borehole at the center of the sample (mimicking a leakage pathway within the wellbore cement in geological CO2 storage environment) was limited. Comparison between acidification and carbonation results in this study shows formation of a thick carbonate layer due to cement carbonation, and this layer was not observed in the acidification result. As for different curing conditions of cement samples, no significant difference in cement alteration depth was observed for the acidification case. For the carbonation case, precipitations in the borehole occurred in the cement sample cured at ambient pressure, while the cement sample cured at high pressure did not produce any precipitation in the borehole. This study provides valuable information on how low pH-induced corrosion and HCO3--induced cement carbonation contribute to structure evolution of wellbore cement in SO42--bearing brine under geological CO2 storage environment.
A Decision-Support Software to Improve the Standard Care in Chinese Type 2 Diabetes
Authors: Luo Yingying , Zhu Yongzan , Chen Jing , Gao Xueying , Yang Wenjia , Zou Xiantong , Zhou Xianghai , Ji Linong
Published: November 2019

Background. To develop a decision-support software according to the Chinese Diabetes Society guideline in order to improve the standard care in type 2 diabetes. Methods. Firstly, we developed a decision-support software for healthcare professionals. It was an independent software on a tablet to record the data of patients and treatments given by their physicians. A major function of the software was to remind doctors when and how they should implement the standard care as recommended by the Chinese Diabetes Society guideline. Secondly, we compared the baseline data of standard care including statin and aspirin usage with data from a previous “3B study” to see whether there was an improvement of these standard cares. Finally, we further compared the data during four quarters of the whole year to evaluate whether there was a continuous improvement. Results. During the first quarter, 27,291 cases and 27,352 cases were collected with complete information about statin and aspirin usage, respectively. The percentage of patients treated with statins and aspirin in our study was significantly higher than that reported in the 3B study (59.6% vs. 19.9% and 59.8% vs. 18.5%, P<0.001). There were no significant differences among the four quarters for the percentage of the patients who were taking statin or aspirin (P>0.05). Conclusion. Our decision-support software has been shown to be effective in continuously improving the standardization of comprehensive treatment in type 2 diabetes.
Information Spreading on Weighted Multiplex Social Network
Authors: Zhu Xuzhen , Ma Jinming , Su Xin , Tian Hui , Wang Wei , Cai Shimin
Published: November 2019

Information spreading on multiplex networks has been investigated widely. For multiplex networks, the relations of each layer possess different extents of intimacy, which can be described as weighted multiplex networks. Nevertheless, the effect of weighted multiplex network structures on information spreading has not been analyzed comprehensively. We herein propose an information spreading model on a weighted multiplex network. Then, we develop an edge‐weight‐based compartmental theory to describe the spreading dynamics. We discover that under any adoption threshold of two subnetworks, reducing weight distribution heterogeneity does not alter the growth pattern of the final adoption size versus information transmission probability while accelerating information spreading. For fixed weight distribution, the growth pattern changes with the heterogeneous of degree distribution. There is a critical initial seed size, below which no global information outbreak can occur. Extensive numerical simulations affirm that the theoretical predictions agree well with the numerical results.
Performance Analysis for the Magnetically Coupled Resonant Wireless Energy Transmission System
Authors: Liu Jinguo , Zhang Xuebin , Yu Jiahui , Xu Zhenyao , Ju Zhaojie
Published: November 2019

As a new wireless energy transmission technology, magnetically coupled resonant wireless energy transmission system (MCRETS) is not easily affected by obstacles in the transmission process, and the transmission distance is relatively far. However, how to balance the relationship between transmission efficiency and power to achieve optimal performance is still a huge challenge. In addition, few studies have theoretically investigated the factors affecting the wireless energy transmission system to obtain an optimal solution. Here, through unprecedented theoretical analysis, we find the exact parameters of system optimization and verify them by simulation and experiments. First, the optimal topology of MCRETS is obtained through theoretical analysis and comparison of topologies. Second, to improve the transmission performance of MCRETS, its impact factors, including transmission distance, resonant frequency, relay coil, and relative position of launch and receiving coils, are analyzed in detail to get accurate parameters. Furthermore, based on the analysis, we propose an unprecedented concept for balancing optimal efficiency and power, which is named the power product. Finally, the effectiveness of the proposed method is verified through analysis and experimental results. These findings shed light on the relationship between efficiency and power and provide a comprehensive theoretical basis for subsequent research.
Significance of Early Postoperative Arterial Lactic Acid, Inferior Vena Cava Variability, and Central Venous Pressure in Hypovolemic Shock
Authors: Lin Wei , Lin Xingsheng , Zhuang Yingfeng , Pan Xiaobin , Wu Chao , Zhang Shujuan , Zhang Lihui , Lin Jian , Shi Songjing , Shi Songchang
Published: November 2019

Introduction. Up to one-third of patients admitted to the ICU are in circulatory shock, and early recognition of the condition is vital if subsequent tissue injuries are to be avoided. We would like to know what role the arterial lactic acid, inferior vena cava variability, and CVP (central venous pressure) play in the early stages of shock. Methods. This is a retrospective study of patients who underwent surgical resuscitation in the Department of Critical Care Medicine. We use the ROC (receiver-operating characteristic) curve to evaluate the significance of each indicator in the diagnosis. For correlation analysis between groups, we first use linear regression for processing and then analysis with correlation. Results. The ROC curve analysis shows that the area under the curve of the lactic acid group was 0.9272, the area under the curve of the inferior vena cava variability group was 0.8652, and the area under the curve of the CVP group was 0.633. Correlation analysis shows that the inferior vena cava variability and arterial lactic acid Pearson’s r = 0.2863 and CVP and arterial lactic acid Pearson’s r = 0.0729. Conclusion. The diagnostic value of arterial lactate is still very high and can still be used as an early warning indicator to help clinicians be alert to the microcirculatory disorders that have emerged quietly. The degree of inferior vena cava variability is linearly related to arterial lactic acid and can also be used as a reference indicator for early evaluation of shock. The diagnostic value of CVP is obviously lower.
Analysis of the Potential for a Hillside Collapse for a Community in Changhua County, Taiwan
Authors: Liu Pei , Tsai Tung-Hua , Peng Szu-Hsien
Published: November 2019

To create communities that are resistant to disasters, public disaster prevention and response must be reinforced by promoting disaster prevention and knowledge and technology to ensure an adequate response through public participation. Promoting disaster prevention measures reduces the number of factors in communities that pertain to disasters. Changhua County contains 589 villages, 81 of which are prone to hillsides (including protected forest). In addition to original potential debris flow torrent communities, disaster‐resistant communities have been established under the guidance of Soil and Water Conservation Bureau (SWCB), Council of Agriculture in Taiwan; Changhua County Government also plans to establish disaster‐resistant communities in other hillside communities. This study proposes an expert questionnaire to determine the potential for a hillside disaster and uses an analytical hierarchy process (AHP) and an analytical network process (ANP) to determine the weights of factors that pertain to potential disasters in hillside communities so that these communities can become resistant to disasters.
Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance
Authors: Schultheis Johanna , Beckmann Dirk , Mulac Dennis , Müller Lena , Esselen Melanie , Düfer Martina
Published: November 2019

Influencing the redox balance of pancreatic beta cells could be a promising strategy for the treatment of diabetes. Nuclear factor erythroid 2p45-related factor 2 (Nrf2) is present in beta cells and regulates numerous genes involved in antioxidant defense. As reactive oxygen species (ROS) are important for beta cell signaling but induce oxidative stress when present in excess, this study elucidates the influence of Nrf2-activating compounds on different kinds of ROS and correlates changes in redox balance to effects on mitochondrial function, insulin release, and cell viability. Acute glucose stimulation (15 mmol/L) of murine islet cells of C57Bl/6N mice affects ROS and redox status of the cells differently. Those ROS monitored by dihydroethidium, which detects superoxide radical anions, decrease. By contrast, oxidant status, monitored by dichlorodihydrofluorescein, as well as intracellular H2O2, increases. Glucolipotoxicity completely prevents these fast, glucose-mediated alterations and inhibits glucose-induced NAD(P)H production, mitochondrial hyperpolarization, and ATP synthesis. Oltipraz (10 μmol/L) or dimethyl fumarate (DMF, 50 μmol/L) leads to nuclear accumulation of Nrf2, restores mitochondrial activity and glucose-dependent ROS turnover, and antagonizes glucolipotoxicity-induced inhibition of insulin release and apoptosis. Importantly, these beneficial effects only occur when beta cells are challenged and damaged by high lipid and carbohydrate supply. At physiological conditions, insulin release is markedly reduced in response to both Nrf2 activators. This is not associated with severe impairment of glucose-induced mitochondrial hyperpolarization or a rise in apoptosis but coincides with altered ROS handling. In conclusion, Nrf2 activators protect beta cells against glucolipotoxicity by preserving mitochondrial function and redox balance. As our data show that this maintains glucose-stimulated insulin secretion, targeting Nrf2 might be suited to ameliorate progression of type 2 diabetes mellitus. By contrast, nonstressed beta cells do not benefit from Nrf2 activation, thus underlining the importance of physiological shifts in ROS homeostasis for the regulation of beta cell function.
Fibrinogen-to-Albumin Ratio Predicts Contrast-Induced Nephropathy in Patients after Emergency Percutaneous Coronary Intervention
Authors: You Zhebin , Guo Tailin , Lin Fan , Lin Chunjin , Chen Jiankang , Li Xiaoming , Chen Yan , Lin Kaiyang
Published: November 2019

Background. The aim of the present study was to investigate the association between fibrinogen-to-albumin ratio (FAR) with contrast-induced nephropathy (CIN) in patients undergoing emergency percutaneous coronary intervention (PCI). Methods. 565 patients with emergency PCI were consecutively enrolled. The primary outcome was CIN defined as either a 25% increase in baseline serum creatinine levels or a 0.5 mg/dL (44 μmol/L) increase in absolute serum creatinine levels within 72 h after the contrast medium exposure. Logistic regression analysis was applied to analyze whether FAR was an independent risk factor for CIN. Results. Overall, 29 (5.1%) patients developed CIN. Compared with the patients without CIN, the patients developing CIN had lower albumin (39.79 ± 3.95 vs. 37.14 ± 5.21, P=0.012) and higher fibrinogen levels (3.51 ± 0.94 vs. 4.14 ± 0.96, P<0.001). In the multivariate logistic analysis, FAR was an independent predictor of CIN (OR = 3.97; 95% CI, 1.61–9.80; P=0.003) along with perihypotension, age >75 years, and LVEF <45%, and 0.106 was the optimal cutoff value of preprocedural FAR to predict CIN. Conclusion. Preprocedural levels of FAR were associated with CIN in patients after emergency PCI.
Acute Exposure to Permethrin Modulates Behavioral Functions, Redox, and Bioenergetics Parameters and Induces DNA Damage and Cell Death in Larval Zebrafish
Authors: Nunes Mauro Eugênio Medina , Schimith Lucia Emanueli , da Costa-Silva Dennis Guilherme , Lopes Andressa Rubim , Leandro Luana Paganotto , Martins Illana Kemmerich , de Mello Renata Siqueira , Hartmann Diane Duarte , de Carvalho Nelson Rodrigues , da Rosa Pamela Carvalho , Trevisan Rafael , Di Giulio Richard Thomas , Posser Thaís , Franco Jeferson Luis
Published: November 2019

Permethrin (PM) is a synthetic pyrethroid insecticide widely used as domestic repellent. Damage effects to nontarget organisms have been reported, particularly in the early stages of development. Studies indicate redox unbalance as secondary PM effect. Therefore, our goal was to investigate the acute PM effects on larval zebrafish. Larvae (6 days postfertilization) were exposed to PM (25–600μg/L) during 24 hours, and 50% lethal concentration was estimated. For subsequent assays, the sublethal PM concentrations of 25 and 50μg/L were used. PM increased anxiety-like behaviors according to the Novel Tank and Light-Dark tests. At the molecular level, PM induced increased ROS, which may be related to the increased lipid peroxidation, DNA damage, and apoptosis detected in PM-exposed organisms. In parallel, upregulation of the antioxidant system was detected after PM exposure, with increased superoxide dismutase, glutathione S-transferase and glutathione reductase activities, and thiol levels. The increased of Nrf2 target genes and the activation of an electrophile response element-driven reporter Tg(EPRE:LUC-EGFP) suggest that the Nrf2 pathway can mediate a fast response to PM, leading to antioxidant amplification. By using high-resolution respirometry, we found that exposure to PM decreased the oxygen consumption in all respiratory stages, disrupting the oxidative phosphorylation and inhibiting the electron transfer system, leading to decrease in bioenergetics capacity. In addition, PM led to increases of residual oxygen consumption and changes in substrate control ratio. Glucose metabolism seems to be affected by PM, with increased lactate dehydrogenase and decreased citrate synthase activities. Taken together, our results demonstrated the adverse effects of acute sublethal PM concentrations during larval development in zebrafish, causing apparent mitochondrial dysfunction, indicating a potential mechanism to redox unbalance and oxidative stress, which may be linked to the detected cell death and alterations in normal behavior patterns caused by acute PM exposure.
Optical Evaluation of New Designs of Multifocal Diffractive Corneal Inlays
Authors: Montagud-Martínez Diego , Ferrando Vicente , Monsoriu Juan A. , Furlan Walter D.
Published: November 2019

Purpose. To assess the imaging properties of two different designs of a new concept of corneal inlays whose working principle is based on diffraction. Methods. The quality of the retinal images provided by Diffractive Corneal Inlays (DCIs) was evaluated theoretically in comparison with Small Aperture Corneal Inlay (SACI). ZEMAX OpticStudio software was employed for the simulations in an eye model with different pupil diameters (3.0 mm and 4.5 mm). The employed merit functions in the analysis were the Modulation Transfer Function (MTF), the area under the MTF (MTFa), and the Point Spread Function (PSF). Comparison was made with the SACI at different defocus conditions. Results. The bifocal nature of the DCIs was demonstrated in a model eye for the first time. It was shown that the intensity of the near focus depends on the radius of the central zone. Retinal image quality of the DCI was equal to or exceeded the SACI in the majority of visual conditions as was demonstrated with simulated images. Conclusions. A new customizable type of corneal inlays has been evaluated using objective numerical simulations. Improvements in imaging of near objects and in light throughput compared with the popular small aperture inlays were demonstrated. These findings open a new technical branch of minimally invasive surgical solutions for the treatment of presbyopia.
Analysis of DES Plaintext Recovery Based on BP Neural Network
Authors: Fan Sijie , Zhao Yaqun
Published: November 2019

Backpropagation neural network algorithms are one of the most widely used algorithms in the current neural network algorithm. It uses the output error rate to estimate the error rate of the direct front layer of the output layer, so that we can get the error rate of each layer through the layer-by-layer backpropagation. The purpose of this paper is to simulate the decryption process of DES with backpropagation algorithm. By inputting a large number of plaintext and ciphertext pairs, a neural network simulator for the decryption of the target cipher is constructed, and the ciphertext given is decrypted. In this paper, how to modify the backpropagation neural network classifier and apply it to the process of building the regression analysis model is introduced in detail. The experimental results show that the final result of restoring plaintext of the neural network model built in this paper is ideal, and the fitting rate is higher than 90% compared with the true plaintext.
Mikroskop-integrierte Optische Kohärenztomographie: Intraoperativer Nutzen bei der Durchführung der subretinalen Gentherapie
Authors: Siebelmann Sebastian
Published: November 2019

In vielen laufenden Studien zu Gentherapien in der Augenheilkunde werden Adeno-assoziierte Viren oder Lentiviren als Vektoren benutzt. Allerdings können diese Vektoren die Retina aufgrund der relativ impermeablen epiretinalen Membran schlecht durchdringen, weswegen das Gen-Therapeutikum vorzugsweise subretinal injiziert wird. Ziel der vorliegenden Studie war es, die subretinale Applikation des AAV-REP1-Gentherapeutikums, bestehend aus einem genetischen Vektor, der auf das Rab-Escort-Protein-1 (REP-1) codierende Gen abzielt (AAV-REP1), mithilfe der Mikroskop-intregrierten Optischen Kohärenztomographie (MI-OCT) durchzuführen.
Diabetische Retinopathie bei Patienten mit Diabetes mellitus
Authors: Simó-Servat Olga , Hernández Cristina , Simó Rafael
Published: November 2019

Die diabetische Retinopathie (DR) ist die häufigste Komplikation von Diabetes mellitus. Hauptrisikofaktoren sind die Krankheitsdauer, schlechte Blutzuckereinstellung und das Vorliegen einer Hypertonie. Allerdings fällt das Risiko sehr unterschiedlich aus, was dafür spricht, dass bei der Entwicklung einer DR andere Faktoren, wie beispielsweise die Erblichkeit oder die glykämische Variabilität eine wichtige Rolle spielen. Einem anderen wichtigen Konzept zufolge handelt es sich bei der DR um einen unabhängigen Prädiktor mikrovaskulärer und makrovaskulärer Komplikationen. Daher muss bei der Bewertung des kardiovaskulären Risikos eines diabetischen Patienten das Vorliegen einer DR berücksichtigt werden. Darüber hinaus kann die Beurteilung der retinalen Neurodegeneration helfen, Diabetiker zu identifizieren, bei denen das Risiko einer kognitiven Einschränkung besteht, einer Komplikation, die bei der Population der Typ-2-Diabetiker zunehmend auftritt. Das Bewusstsein für eine etwaige DR hat bei der Beurteilung diabetischer Patienten auch therapeutische Implikationen. So kann beispielsweise nach einer raschen Verbesserung der Blutzuckerwerte eine Verschlechterung der DR auftreten. Insgesamt enthält die vorliegende Arbeit eine kritische Übersicht über die Bedeutung der DR in der allgemeinen Versorgung von Patienten mit Diabetes.
ДИСЛІПІДЕМІЧНІ ЗМІНИ ЯК ПРЕДИКТОРИ ПРОГРЕСУВАННЯ ЗОВНІШНЬОСЕКРЕТОРНОЇ НЕДОСТАТНОСТІ ПІДШЛУНКОВОЇ ЗАЛОЗИ У ХВОРИХ НА ХРОНІЧНИЙ ПАНКРЕАТИТ
Authors: Arkhij E. J. , Prylypko L. B. , Moskal O. M.
Published: November 2019

Хронічний панкреатит (ХП) відноситься до нозологій, показники захворюваності яких мають тенденцію до загальносвітового зростання. Визначено ряд причин, які сприяють появі та прогресуванню хронічного запального процесу на рівні підшлункової залози (ПЗ). Одними із таких є дисліпопротеїнемії.
Мета дослідження: проаналізувати особливості ліпідного метаболізму у пацієнтів, які страждають на ХП із екзокринною недостатністю.
Матеріали та методи: нами обстежено 79 пацієнтів з ознаками ХП, які знаходилися на стаціонарному лікуванні у Хустській РЛ протягом 2017-2018 років. Відповідно до отриманих результатів було сформовано три досліджувані групи. Першу складали пацієнти на ХП із легкою зовнішньосекреторною недостатністю ПЗ (ЗНПЗ) (n = 50), другу ‒ із помірною ЗНПЗ (n = 29), до третьої включили практично здорових людей (n = 23). Для оцінки екзокринної функції ПЗ визначали рівень еластази-1 у калі. Ліпідний гомеостаз оцінювали за наступними показниками: загальний холестерол (ЗХС), тригліцерол (ТГ), холестерол ліпопротеїнів низької щільності (ХС ЛПНЩ), холестерол ліпопротеїнів дуже низької щільності (ХС ЛПДНЩ), холестерол ліпопротеїнів високої щільності (ХС ЛПВЩ) та індекс атерогенності (ІА). Крім того, провели кореляційний аналіз впливу дисліпідемічних розладів на виразність ЗНПЗ.
Результати досліджень вказують на наявність у хворих на ХП “ліпідного дистрес-синдрому”, що проявлявся у вигляді гіперхолестеролемії, гіпертригліцеролемії, підвищення концентрації ХС ЛПНЩ, ХС ЛПДНЩ та зниження вмісту ХС ЛПВЩ. Встановлено залежність екзокринної недостатності від вираженості дисліпідемічних розладів.
Висновки: у хворих на ХП виявлено ознаки порушень ліпідного метаболізму та доведено вплив останніх на екзокринну функцію ПЗ. Тому вважаємо необхідним ретельне дослідження ліпідограми у всіх пацієнтів із ознаками хронічного ураження ПЗ.
ОСТЕОІНДУКТИВНІ ПРЕПАРАТИ ДЛЯ ЗАМІЩЕННЯ КІСТКОВИХ ДЕФЕКТІВ У СТОМАТОЛОГІЇ
Authors: Duda K. M. , Klishch I. M.
Published: November 2019

В статті вивчено проблему дефіциту кісткової тканини альвеолярного гребеня як ускладнення стоматологічних захворювань, що утруднює подальшу імплантацію. Висвітлено загальні дані про матеріали, які застосовують для заміщення дефектів кісткової тканини в щелепно-лицевій ділянці. Обґрунтовано репаративні властивості матеріалів, що пришвидшують остеоінтеграцію. Проаналізовано позитивні властивості та недоліки препаратів кожної з існуючих груп залежно від походження.

Мета – проаналізувати літературні дані щодо остеоіндуктивних препаратів, які застосовують у стоматології.

Висновок. На сьогоднішній день ще не існує кісткового матеріалу, який би відповідав усім вимогам. Необхідний пошук нових, безпечних, доступних і легких в експлуатації штучних матеріалів, які повинні мати велику амортизаційну здатність, високу витривалість, антимікробну дію і резистентність до інфекції, пористу структуру та інертність до біологічних тканин і не викликати запальних, алергічних і токсичних реакцій.
ВПЛИВ РЕЗЕКЦІЇ РІЗНИХ ОБ’ЄМІВ ПАРЕНХІМИ ПЕЧІНКИ НА ЇЇ ЖОВЧОУТВОРЮВАЛЬНУ ФУНКЦІЮ
Authors: Hnatjuk M. S. , Monastyrska N. Ya. , Tatarchuk L. V.
Published: November 2019

Вступ. На сьогодні в клініках широко виконують резекцію печінки. Видалення великих її об’ємів призводить до розвитку різних пострезекційних ускладнень та змін жовчоутворення.

Мета дослідження – вивчити особливості жовчоутворювальної функції печінки при резекції різних об’ємів її паренхіми.

Методи дослідження. Дослідження проведено на 45 лабораторних статевозрілих білих щурах-самцях, яких поділили на 3 групи: 1-ша нараховувала 15 інтактних тварин; 2-га – 15 щурів після резекції 31,5 % паренхіми печінки; 3-тя – 15 тварин, у яких було видалено 58,1 % об’єму печінки. Через місяць від початку досліду за умов тіопенталового наркозу катетеризували спільну жовчну протоку і проводили забір жовчі протягом 1 год. При цьому розраховували інтенсивність секреції жовчі, в якій визначали концентрацію жовчних кислот: таурохолевої, глікохолевої, холевої, хенодезоксихолевої+дезоксихолевої, вміст фосфоліпідів, вільних жирних кислот, триацилгліцеролів і протеїнів. Евтаназію тварин здійснювали шляхом кровопускання за умов тіопенталового наркозу через місяць від початку експерименту. Гістологічні мікропрепарати печінки досліджували світлооптично. Кількісні показники обробляли статистично.

Результати й обговорення. Резекція 58,1 % паренхіми печінки призводила до пострезекційної портальної гіпертензії, яка характеризувалася розширенням ворітної печінкової вени, повнокров’ям з дилатацією брижових вен, венозного русла тонкої і товстої кишок, асцитом, спленомегалією. Інтенсивність секреції жовчі за досліджуваних умов експерименту знизилася на 28,9 % порівняно з контролем, концентрація таурохолевої кислоти – на 21,5 %, глікохолевої – на 15,56 %, холевої – на 18,6 %, а хенодезоксихолевої+дезоксихолевої – на 16,2 %, концентрація фосфоліпідів – на 11,0 %, вільних жирних кислот – на 10,4 %, триацилгліцеролів – на 19,8 %, протеїнів – на 8,02 %. Світлооптично в мікропрепаратах печінки тварин 3-ї групи спостереження відмічали повнокров’я венозних судин, осередки гіпертрофії, дистрофії гепатоцитів, появу лімфоїдно-гістіоцитарних інфільтратів та збільшення стромальних структур.

Висновок. Резекція лівої і правої бокових часток печінки призводить до пострезекційної портальної гіпертензії та змін жовчоутворення і жовчовиділення, що характеризується зниженням інтенсивності секреції жовчі, концентрації жовчних кислот, фосфоліпідів, вільних жирних кислот, триацилгліцеролів та протеїнів.
Herpetofauna of Parque Estadual Altamiro de Moura Pacheco: one of the last remnants of seasonal forest in the core region of the Brazilian Cerrado
Authors: Ramalho Werther Pereira , França Daniella Pereira Fagundes , Guerra Vinicius , Marciano Rosy , Vale Nilton Carlos Do , Silva Hélder Lúcio Rodrigues
Published: November 2019

Studies in remnants of semi-deciduous seasonal forest of the Cerrado are needed to fill sampling gaps and improve basic knowledge of biodiversity. This study presents data on the herpetofauna of Parque Estadual Altamiro de Moura Pacheco, one of the last protected areas of seasonal forest in the core region of the Brazilian Cerrado. Fourteen sites were sampled between March 2007 and April 2008 using pitfall traps and active searches. A total of 35 anuran species were recorded, most of which were found in hygrophilous environments near forest fragments, open areas and riparian or gallery forest. A total of 29 reptile species were recorded, most of which were found in semi-deciduous forest and riparian or gallery forest. Fourteen of the amphibians and five of the reptiles are endemic to the Cerrado. The richness of amphibians and reptiles found in Parque Estadual Altamiro de Moura Pacheco is regionally representative, with communities typical of forest environments.
Status and distribution of Paraguayan macaws (Aves: Psittacidae) with a new country record
Authors: Rodríguez Oscar , Castillo Leandro , Smith Paul , Del Castillo Hugo
Published: November 2019

Eight species of macaw (Psittacidae: Anodorhynchus, Ara, Primolius) have previously been reported from Paraguay. We discuss all verifiable reports of the species from Paraguay and provide comment on their statuses. Ara chloropterus and Primolius auricollis are both widespread species known from multiple reports across a wide geographic area. We report minor range extensions within Paraguay for both species. Anodorhynchus hyacinthinus is documented as a breeding resident with a restricted distribution in the Upper Paraguay River basin. The first modern records of Ara ararauna and the first record of Diopsittaca nobilis for the country are documented with photographs. We are unable to find any confirmed records of Anodorhynchus glaucus from Paraguay and thus consider it of possible occurrence. Two species are rejected as erroneously cited, Ara militaris and Ara glaucogularis. Consequently six species in four genera are now confirmed to occur in Paraguay.
Spontaneous Atrial Fibrillation in Transgenic Goats With TGF (Transforming Growth Factor)-β1 Induced Atrial Myopathy With Endurance Exercise
Authors: Regouski Misha , Galenko Oxana , Doleac Jason , Olsen Aaron L. , Jacobs Victoria , Liechty Dustin , White Kenneth L. , Bunch T. Jared , Lee Pamela M. , Rutigliano Heloisa M. , Polejaeva Irina A. , Cutler Michael J.
Published: November 2019

Background:

There is increasing evidence that endurance exercise is associated with increased risk of atrial fibrillation (AF). However, it is unknown if the relationship between endurance exercise and AF is dependent on an atrial myopathy.

Methods:

Six cardiac-specific TGF (transforming growth factor)-β1 transgenic and 6 wild-type (WT) goats were utilized for these studies. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using 5 separate 10 s bursts of atrial pacing (160–200 ms). Three months of progressive endurance exercise (up to 90 minutes at 4.5 mph) was performed. Quantitative assessment of circulating microRNAs and inflammatory biomarkers was performed.

Results:

Sustained AF (≥30 s) was induced with 10 s of atrial pacing in 4 out of 6 transgenic goats compared with 0 out of 6 WT controls at baseline (
P
<0.05). No spontaneous AF was observed at baseline. Interestingly, between 2 and 3 months of exercise 3 out of 6 transgenic animals developed self-terminating spontaneous AF compared with 0 out of 6 WT animals (
P
<0.05). There was an increase in AF inducibility in both transgenic and WT animals during the first 2 months of exercise with partial normalization at 3 months (transgenic 67%; 100%; 83% versus WT 0%; 67%; 17%). These changes in AF susceptibility were associated with a decrease in circulating microRNA-21 and microRNA-29 during the first 2 months of exercise with partial normalization at 3 months in both transgenic and WT animals. Finally, MMP9 (matrix metallopeptidase 9) was increased during the second and third months of exercise training.

Conclusions:

This study demonstrates a novel transgenic goat model of cardiac fibrosis (TGF-β1 overexpression) to demonstrate that endurance exercise in the setting of an underlying atrial myopathy increases the incidence of spontaneous AF. Furthermore, endurance exercise seems to increase inducible AF secondary to altered expression of key profibrotic biomarkers that is independent of the presence of an atrial myopathy.