bluuebunny/crossref_metadata_2025 huggingface dataset:
MLN4924 protects against interleukin-17A-induced pulmonary inflammation by disrupting ACT1-mediated signaling
Authors: Hao Rui , Song Yunduan , Li Runsheng , Wu Yaxian , Yang Xinyi , Li Xiaozong , Qian Feng , Ye Richard D. , Sun Lei
Published: March 2019

An excessive inflammatory response in terminal airways, alveoli, and the lung interstitium eventually leads to pulmonary hypertension and chronic obstructive pulmonary disease. Proinflammatory cytokine interleukin-17A (IL-17A) has been implicated in the pathogenesis of pulmonary inflammatory diseases. MLN4924, an inhibitor of NEDD8-activating enzyme (NAE), is associated with the treatment of various types of cancers, but its role in the IL-17A-mediated inflammatory response has not been identified. Here, we report that MLN4924 can markedly reduce the expression of proinflammatory cytokines and chemokines such as IL-1β, IL-6, and CXCL-1 and neutrophilia in a mouse model of IL-17A adenovirus-induced pulmonary inflammation. MLN4924 significantly inhibited IL-17A-induced stabilization of mRNA of proinflammatory cytokines and chemokines in vitro. Mechanistically, MLN4924 significantly blocked the activation of MAPK and NF-κB pathways and interfered with the interaction between ACT1 and tumor necrosis factor receptor-associated factor proteins (TRAFs), thereby inhibiting TRAF6 ubiquitination. Taken together, our data uncover a previously uncharacterized inhibitory effect of MLN4924 on the IL-17A-mediated inflammatory response; this phenomenon may facilitate the development of MLN4924 into an effective small-molecule drug for the treatment of pulmonary inflammatory diseases.
Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats
Authors: Li Qing-Chun , Liang Yun , Su Zhen-Bo
Published: March 2019

The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H2O2, and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.
Low guanylyl cyclase activity in Weddell seals: implications for peripheral vasoconstriction and perfusion of the brain during diving
Authors: Hindle Allyson G. , Allen Kaitlin N. , Batten Annabelle J. , Hückstädt Luis A. , Turner-Maier Jason , Schulberg S. Anne , Johnson Jeremy , Karlsson Elinor , Lindblad-Toh Kerstin , Costa Daniel P. , Bloch Donald B. , Zapol Warren M. , Buys Emmanuel S.
Published: March 2019

Nitric oxide (NO) is a potent vasodilator, which improves perfusion and oxygen delivery during tissue hypoxia in terrestrial animals. The vertebrate dive response involves vasoconstriction in select tissues, which persists despite profound hypoxia. Using tissues collected from Weddell seals at necropsy, we investigated whether vasoconstriction is aided by downregulation of local hypoxia signaling mechanisms. We focused on NO–soluble guanylyl cyclase (GC)-cGMP signaling, a well-known vasodilatory transduction pathway. Seals have a lower GC protein abundance, activity, and capacity to respond to NO stimulation than do terrestrial mammals. In seal lung homogenates, GC produced less cGMP (20.1 ± 3.7 pmol·mg protein−1·min−1) than the lungs of dogs (−80 ± 144 pmol·mg protein−1·min−1less than seals), sheep (−472 ± 96), rats (−664 ± 104) or mice (−1,160 ± 104, P < 0.0001). Amino acid sequences of the GC enzyme α-subunits differed between seals and terrestrial mammals, potentially affecting their structure and function. Vasoconstriction in diving Weddell seals is not consistent across tissues; perfusion is maintained in the brain and heart but decreased in other organs such as the kidney. A NO donor increased median GC activity 49.5-fold in the seal brain but only 27.4-fold in the kidney, consistent with the priority of cerebral perfusion during diving. Nos3 expression was high in the seal brain, which could improve NO production and vasodilatory potential. Conversely, Pde5a expression was high in the seal renal artery, which may increase cGMP breakdown and vasoconstriction in the kidney. Taken together, the results of this study suggest that alterations in the NO-cGMP pathway facilitate the diving response.
Discharge properties of morphologically identified vestibular neurons recorded during horizontal eye movements in the goldfish
Authors: Pastor A. M. , Calvo P. M. , de la Cruz R. R. , Baker R. , Straka H.
Published: March 2019

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (eIIhI) or vice versa (eIhII). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant eIIhI subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in eIhII cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network.

NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi.
Prevalence of Age-Associated Testosterone Deficiency Syndrome in Indian Population
Authors: Yadav Ghanendra Kumar , Pahwa Mrinal , Singh Mahendra , Tyagi Vipin , Chadha Sudhir
Published: March 2019

Testosterone deficiency syndrome (TDS) is a gradual age-related phenomenon that occurs in a large proportion of the aging male population. This current prospective study was done with the objective to estimate the prevalence of age-associated TDS in India and its clinical profile. A total of 800 male patients aged ≥40 year were approached to participate in the study. A brief history and focused examination was done. Based on our exclusion criteria, 55 patients were excluded. Androgen deficiency in aging male (ADAM) questionnaire was administered to all remaining 745 patients. Out of these 745 patients, ADAM-positive (symptomatic TDS) patients were found to be 359 and enrolled in the study. In all ADAM-positive patients, serum testosterone levels were measured. Prevalence of symptomatic TDS in study population was found to be 48.18%. Mean total and free testosterone level of symptomatic TDS population were 3.287 ± 1.494 ng/ml (1.12–9.61) and 7.476 ± 2.902 pg/ml (2.18–21.76), respectively. Prevalence of biochemically confirmed TDS among symptomatic TDS population was 60.17%. Prevalence of TDS increases progressively with each decade of life (p=0.034). Prevalence was higher in patients with diabetes, hypertension, coronary artery disease, obesity, and metabolic syndrome. TDS is a real phenomenon with a prevalence of 28.99% in our study population.
Kinase Inhibitors of Novel Pyridopyrimidinone Candidates: Synthesis and In Vitro Anticancer Properties
Authors: Khalifa Nagy M. , Al-Omar Mohamed A. , Alkahtani Hamad M. , Bakheit Ahmed H.
Published: March 2019

A new class of pyridopyrimidinone compounds containing different nitrogenous heterocycles were synthesized starting from the key precursor 2-hydrazinyl-5-phenyl-7-(pyridin-3-yl)pyrido[2,3-d]pyrimidin-4(3H)-one via condensation with series of aromatic aldehydes and cyclization using different reagents as ethyl acetoacetate, ethyl cyanoacetate, diethyl malonate, and ammonium isothiocyanate. The bioassay results showed compound 6 to be highly effective towards three human cancer cell lines (HepG2, PC-3, and HCT-116) in vitro with promising activity values (IC50: 0.5 μM) relative to the standard doxorubicin (IC50: 0.6 μM). Kinase inhibitory evaluation of compound 6 displays hopeful inhibitory action against BRAF V600E, EGFR, and PDGFRβ at100 μM. The molecular docking studies supported the initial kinase assay.
Novel Removal of Diazinon Pesticide by Adsorption and Photocatalytic Degradation of Visible Light-Driven Fe-TiO2/Bent-Fe Photocatalyst
Authors: Phuong Nguyen Minh , Chu Ngoc Chau , Van Thuan Doan , Ha Minh Ngoc , Hanh Nguyen Thi , Viet Huong Do Thi , Minh Thu Nguyen Thi , Van Quan Pham , Thanh Truc Nguyen Thi
Published: March 2019

In the study, Fe was used as a dopant to enhance photocatalytic activity of TiO2. Then, the Fe-doped TiO2 was deposited on bentonite, which was pillared by Fe. The synthesized materials were characterized by SEM, XRD, UV-Vis, BET, and point of zero charge (pHPZC). Then, the synthesized materials were used for diazinon removal under both dark and visible light conditions to investigate adsorption and photocatalytic degradation abilities of the synthesized materials. The maximum diazinon adsorption capacity of the synthesized Fe-TiO2/Bent-Fe was 27.03 mg/g. The obtained results indicated that the Fe-TiO2/Bent-Fe exhibited high photocatalytic degradation activity for removal of diazinon even under visible light. The diazinon removal experiments were also conducted using different photocatalyst dosages, under different pH and light sources to figure the optimal conditions for removal processes. The obtained results indicated that optimal photocatalyst dosage and pH were 0.5 g/L and 4.5, respectively. Finally, the natural light generated from solar could be suitable used for diazinon removal by the synthesized Fe-TiO2/Bent-Fe.
Sputum Smear Positive Pulmonary Tuberculosis Diagnostic Dropout Rate in Public Health Facilities, Addis Ababa, Ethiopia
Authors: Desalegn Daniel Melese , Kitila Kumera Terfa , Taddese Boja Dufera , Hailu Tinsae Kidanemariam , Dinku Tariku Takle , Asferie Kassahun Demisse , Balcha Hanna Mekonnen , Gebeyehu Chalachew Sisay , Medhin Girmay
Published: March 2019

Background. Prolonged laboratory diagnostic process of tuberculosis can lead to failure to complete the diagnosis and increase dropout rate of smear positive pulmonary tuberculosis (PTB) cases. This implies such dropout patients without completing diagnosis are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. The aim of this research is to determine the level of smear positive PTB diagnosis dropout rate of spot-morning-spot sputum microscopy diagnosis method in public health facilities, in Addis Ababa, Ethiopia. Methods. Retrospective review of patient documents in 13 public health facilities’ TB laboratory in Addis Ababa was conducted from October 2011 to March 2016. Data was computerized using Epi-info software and analysed using SPSS version 20.0 software. Descriptive numerical summaries were used to present the findings. Association between the dropout rate and demographic variables was assessed by Chi-square (X2). Bivariate model using Odds Ratio (OR) with a 95% Confidence Interval (CI) was calculated. P-Value less than 0.05 was taken as statistically significant. Results. Of 41,884 presumptive TB patients registered during the 53 months for laboratory investigation, 5.9% were positive for the first spot sputum smear microscopy. Among these positive cases, 142 (5.8%) and 298 (12.1%) did not come back to the laboratory to submitted early morning and second spot sputum specimens, respectively. The diagnostic dropout for morning sputum specimen in hospitals was 5.6% (58/1039) and in health centres was 5.9% (84/1424). However, higher proportion of dropout for second spot sputum specimen in hospitals was 16.4% (170/1039), compared to the health centres, 8.9% (128/1424). Diagnostic dropout of sputum smear microscopy had no significant association with sociodemographic variable (P value >0.05), while it had significant association with facility type (P value <0.05). Conclusion. In this study smear positive pulmonary tuberculosis diagnostic dropout rate was high compared to WHO reported for the new strategy shift implying the importance of shifting to same-day approach. Hence, shifting from conventional to same day is crucial to minimize the TB diagnostic dropout rate in the study area and other similar settings. Further research is needed/recommended in the local setting to compare the yield and dropout rates between same-day and conventional sputum smear microscopy approach.
Modeling and Optimization for Automobile Mixed Assembly Line in Industry 4.0
Authors: Gong Lixiong , Zou Bingqian , Kan Zhiqun
Published: March 2019

Industry 4.0 promotes the development of traditional manufacturing industry to digitization, networking, and intellectualization. Smart factory is composed of network that includes production equipment, robot, conveyor, and logistics system. According to the characteristics of the mixed flow assembly, a simulation platform of automobile mixed flow assembly is built based on industry 4.0 in the paper, which operates and manages automobile assembly, logistics warehouse, and CPS effectively. On this basis, FlexSim software is adopted to establish the auto-mixed assembly model that finds out the bottleneck of auto-mixed assembly problem. By means of parameter adjustment, rearrangement, and merger of process, the whole assembly time of the 500 automobiles dropped by 33 hours, the equipment utilization rate increased by 20.19%, and the average blocked rate decreased by 21.19%. The optimized results show that the proposed model can greatly increase manufacturing efficiency and practical application in industry 4.0.
Preventive Effect of the Herbal Preparation, HemoHIM, on Cisplatin-Induced Immune Suppression
Authors: Kim Seul-Ki , Kwon Da-Ae , Lee Hak Sung , Kim Hyun Kyu , Kim Won-Ki
Published: March 2019

We determined the functional effect of the herbal preparation, HemoHIM, on the immune system, by examining the immunomodulatory activities of HemoHIM using immunocompromised mice. In this study, to examine the effect on the restoration of immune cells and balance in the immune system, we utilized a cisplatin-induced immunosuppression mouse model. Mice were injected intraperitoneally with cisplatin, an immunosuppressive anticancer, and then received oral doses of 100, 250, and 500 mg/kg of HemoHIM for 14 days. The HemoHIM prevented the cisplatin-induced loss of body and organ weight. In terms of innate immunity, natural killer (NK) cell activity and phagocytosis increased in the HemoHIM group compared to the cisplatin control group. The HemoHIM group also showed a significantly higher expression of Th1-mediated cytokines (interferon gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α)) and inhibited the production of Th2-mediated cytokine interleukin-4 (IL-4) compared to cisplatin control group. These findings indicate that HemoHIM enhances immune activity by modulating immune cell activity and cytokine secretion in immune-suppressed mice.
Neuroprocessing Mechanisms of Music during Fetal and Neonatal Development: A Role in Neuroplasticity and Neurodevelopment
Authors: Chorna O. , Filippa M. , De Almeida J. Sa , Lordier L. , Monaci M. G. , Hüppi P. , Grandjean D. , Guzzetta A.
Published: March 2019

The primary aim of this viewpoint article is to examine recent literature on fetal and neonatal processing of music. In particular, we examine the behavioral, neurophysiological, and neuroimaging literature describing fetal and neonatal music perception and processing to the first days of term equivalent life. Secondly, in light of the recent systematic reviews published on this topic, we discuss the impact of music interventions on the potential neuroplasticity pathways through which the early exposure to music, live or recorded, may impact the fetal, preterm, and full-term infant brain. We conclude with recommendations for music stimuli selection and its role within the framework of early socioemotional development and environmental enrichment.
Loxoscelism: Cutaneous and Hematologic Manifestations
Authors: Nguyen Ngan , Pandey Manjari
Published: March 2019

Background. Brown recluse spider (BRS) envenomation can lead to significant morbidity through severe local reaction and systemic illness including acute hemolytic anemia, rhabdomyolysis, disseminated intravascular coagulopathy (DIC), and even death. We aim to describe the clinical features and the roles of antibiotics and steroids in the treatment of loxoscelism. Methods. We retrospectively identified nine patients (pts) at our institution who were admitted with moderate to severe loxoscelism. A chart review was performed to highlight important clinical features and effect of interventions. Results. Nine pts (age 18 to 53) presented with fever (6), rash (9), pain/swelling (4), and jaundice (2). Of these, 6 pts had antecedent spider bites documented. Five pts were discharged from Emergency Room (ER) with oral antibiotics for “cellulitis” and were readmitted with severe systemic symptoms, with almost half (45%) of the pts being admitted to the intensive care unit. The most common admission diagnosis was sepsis secondary to cellulitis (6). Four pts developed worsening dermonecrosis, and 3 received prompt incision and drainage (I&D) with debridement. Hemolytic anemia developed around day 5 after spider bite (average); the lowest mean hemoglobin level was 5.8g/dL, with average drop of 3.1 g/dL. Direct antiglobulin test (DAT) (for both complement and surface immunoglobulin) was positive in 4 out of 9 patients. Four pts received glucocorticoid therapy for their hemolytic anemia. The use of steroid and intravenous immunoglobulin (IV Ig) did not seem to show a difference in the time of recovery although those who received steroids required less blood transfusion (2.1 units less). All pts had a complete recovery within two weeks. Conclusion. Treatment of systemic loxoscelism involves aggressive supportive care including appropriate wound management, blood transfusions, intravenous fluid replacement, and appropriate antibiotic coverage. It is unclear at this time if glucocorticoids or IVIg has any beneficial impact on the treatment of severe loxoscelism.
Myotonic Dystrophy and Anesthetic Challenges: A Case Report and Review
Authors: Mangla Chanchal , Bais Kimmy , Yarmush Joel
Published: March 2019

Providing anesthesia to patients with myotonic dystrophy (DM) can be very challenging due to the multisystemic effects of the disease and extreme sensitivity of these patients to sedatives, opioids, and anesthetic agents. Other factors such as hypothermia, shivering, or mechanical or electric stimulation during surgery can precipitate myotonia which is difficult to abolish and can lead to further complications. Generally, local or regional anesthesia is preferred to avoid the complications associated with general anesthesia in this group. However there are several case reports of successful use of general anesthesia (with or without volatile agents and with or without opioids). These general anesthetic cases led to postoperative admission to the regular floor or ICU. We present a case of a woman with a history of DM who underwent robotic assisted laparoscopic hysterectomy under general anesthesia and was discharged home on the same day.
A Stochastic Approach to Energy Cost Minimization in Smart-Grid-Enabled Data Center Network
Authors: Ghassemi Abolfazl , Goudarzi Pejman , Mirsarraf Mohammad R. , Gulliver T. Aaron
Published: March 2019

We propose a Lyapunov drift-plus-penalty- (LDPP-) based algorithm to optimize the average power cost for a data center network. In particular, we develop an algorithm to minimize the operational cost using real-time electricity pricing with the integration of green energy resources from the smart grid. The LDPP technique can achieve significant energy cost savings under quality of service (QoS) constraints. Numerical results are presented to evaluate and validate our solution. These results illustrate significant operational/energy cost reductions for a data center network over the conventional approach which optimizes the predicted values of stochastic parameters under a fixed QoS constraint.
Experimental Investigation on Mechanical Properties of Hybrid Steel and Polyethylene Fiber-Reinforced No-Slump High-Strength Concrete
Authors: Yuan Tian-Feng , Lee Jin-Young , Min Kyung-Hwan , Yoon Young-Soo
Published: March 2019

This paper presents experimental investigations on the mechanical properties of no-slump high-strength concrete (NSHSC), such as the compressive and flexural strength. First, to determine the proper NSHSC mixtures, the compressive and flexural strength of three different water-to-binder ratios (w/b) of specimens with and without polyethylene (PE) fiber was tested at test ages. Then, the effect of hybrid combinations of PE fiber and steel fiber (SF) on the compressive strength, flexural strength, flexural toughness, and flexural energy dissipation capacity was experimentally investigated. Furthermore, the various hybrid fiber-reinforced NSHSCs were evaluated, and their synergy was calculated, after deriving the benefits from each of the individual fibers to exhibit a synergetic response. The test results indicate that a w/b of 16.8% with or without fibers had lower strength and flexural strength (toughness) than those of other mixtures (w/b of 16.4% and 17.2%). Specimens with a hybrid of SF and short PE fibers exhibited a higher compressive and flexural strength, flexural toughness, energy dissipation capacity, and fiber synergy in all considered instances.
The Prevalence and Health Impacts of Frequent Work Discrimination and Harassment among Women Firefighters in the US Fire Service
Authors: Jahnke Sara A. , Haddock Christopher K. , Jitnarin Nattinee , Kaipust Christopher M. , Hollerbach Brittany S. , Poston Walker S. C.
Published: March 2019

Intro. Both discrimination and harassment directly impact mental and physical health. Further, workplace discrimination degrades workplace culture and negatively impacts health behaviors, job-related outcomes, and family dynamics. Women represent a small proportion of the fire service and are often the targets of discrimination/harassment, yet little research documents the impact of such experiences. The purpose of this study was to evaluate the relationship between chronic work discrimination and/or harassment and women firefighters’ (FFs) physical and mental health, substance abuse, and job efficacy, stress, and satisfaction. Methods. Snowball sampling was used to solicit participation from women career FFs. Participants completed an online survey regarding physical and mental health, health behavior, job efficacy/stress/satisfaction, and family well-being. Logistic regression examined the impact of work discrimination-harassment severity on dichotomous variables. Results. 1,773 had complete data on their experiences with work-related discrimination and harassment. Women reported experiencing verbal (37.5%) and written (12.9%) harassment, hazing (16.9%), sexual advances (37.4%), and assaults (5.1%) in the fire service. FFs in the highest tertile of work discrimination-harassment severity reported over 40% more poor health days in the last 30 days (OR=1.42; 95%CI=1.33-1.51; p<0.001). Women who experienced moderate and severe discrimination/harassment had negative mental health outcomes including higher prevalence of depressive symptoms, anxiety, and PTSD symptoms. Those who experienced high rates of discrimination and/or harassment also were more likely to report issues with alcohol consumption. Conclusion. The impact of discrimination and harassment, related negative physical and mental outcomes, low levels of job satisfaction, and negative impact of these experiences on family/home stress likely take a significant toll on women in the fire service. Findings confirm and extend previous work suggesting there is a need to improve the mental and physical health of women FFs. Future work should examine the prospective relationship between discrimination/harassment and poor health outcomes and potential policies/practices to reduce these negative behaviors.
Multimodal OCT Reflectivity Analysis of the Cystoid Spaces in Cystoid Macular Edema
Authors: Farci Roberta , Sellam Alexandre , Coscas Florence , Coscas Gabriel J. , Diaz Giacomo , Napoli Pietro Emanuele , Souied Eric , Galantuomo Maria Silvana , Fossarello Maurizio
Published: March 2019

Purpose. To compare and evaluate images of macular cysts with different degrees of reflectivity (from gray to black signal) as observed in B scan spectral domain OCT (SDOCT) and EnFace OCT with decorrelation signal obtained with OCT-angiography (OCTA) in eyes with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) and retinal vein occlusion (RVO). Methods. Images from 3033 patients affected by CME secondary to diabetes or RVO examined OCTA (Optovue XR Avanti, Optovue, USA) at the University Eye Clinic of Créteil, Hôpital Intercommunal, France, and at the University Eye Clinic of Cagliari, “San Giovanni di Dio” Hospital, Italy, were retrospectively examined. The deep capillary plexus OCTA images and the corresponding EnFace OCT images, both acquired with the same automatic segmentation, had been overlapped to compose RGB color images as red and green channels, respectively, using ImageJ software (National Institutes of Health, Bethesda, MD). Afterward, linear regions of interest were traced on the color images to obtain the profiles of OCTA and EnFace gray values. Number of pixels, mean gray value and standard deviation of the area traced in OCT-A, and EnFace image were analyzed and statistically correlated. Data were exported to Excel to create the plots. Results. 94 patients with DME and 27 patients with RVO showed intraretinal macular cystoid spaces with similar homogeneous, gray-looking content; 73 patients with DME and 113 patients with RVO showed macular cystoid spaces with homogeneous, black-looking content, as observed at SD-OCT, EnFace and OCTA scans. Interestingly, the limits of macular cystoid spaces were clearly detectable with OCTA. The analysis of red and green profiles demonstrated a clearly visible overlap between average OCTA and EnFace signal observed around cystoid spaces that could be attributed to a relationship between the dynamic vascularization and the structural density of the tissue. Conclusions. This is the first investigation that characterizes and correlates OCTA and EnFace signals on images of macular cystoid spaces in DR and RVO. The low intensity OCTA signals observed inside cystoid spaces raise a relevant question about their nature, as to whether they are due to the presence of corpusculated material pouring out from bloodocular-barrier or they should be considered OCTA artifacts.
The Immunomodulatory Effect of Alpha-Lipoic Acid in Autoimmune Diseases
Authors: Liu Wei , Shi Lian-jie , Li Sheng-guang
Published: March 2019

Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested thatα-lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects ofα-lipoic acid. It highlights the fact thatα-lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.
Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease
Authors: Kong Danli , Yan Yan , He Xiao-Yi , Yang Huihuang , Liang BiYu , Wang Jin , He Yuqing , Ding Yuanlin , Yu Haibing
Published: March 2019

Objective. To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer’s disease (AD) mouse model. Methods. First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERβ, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid β protein (Aβ) in brain tissue. Results. Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERβ in the brain tissue at the mRNA and protein levels and the expression of Aβ in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. Conclusion. Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.
Efficacy Evaluation and Tracking of Bone Marrow Stromal Stem Cells in a Rat Model of Renal Ischemia-Reperfusion Injury
Authors: Wang Ling-Jie , Yan Chang-Ping , Chen Dan , Xu Ting , He Sheng , Zhang Hua , Xu Cheng , Qiao Ying , Jiang Zeng-Yu , Zhang Rui-Ping , Li Jian-Ding
Published: March 2019

Objectives. The aim of this study was to evaluate the effects of bone marrow stromal stem cells (BMSCs) on renal ischemia-reperfusion injury (RIRI) and dynamically monitor engrafted BMSCs in vivo for the early prediction of their therapeutic effects in a rat model. Methods. A rat model of RIRI was prepared by clamping the left renal artery for 45 min. One week after renal artery clamping, 2 × 106 superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected into the renal artery. Next, MR imaging of the kidneys was performed on days 1, 7, 14, and 21 after cell transplantation. On day 21, after transplantation, serum creatinine (Scr) and urea nitrogen (BUN) levels were assessed, and HE staining and TUNEL assay were also performed. Results. The body weight growth rates in the SPIO-BMSC group were significantly higher than those in the PBS group (P < 0.05), and the Scr and BUN levels were also significantly lower than those in the PBS group (P < 0.05). HE staining showed that the degree of degeneration and vacuole-like changes in the renal tubular epithelial cells in the SPIO-BMSC group was significantly better than that observed in the PBS group. The TUNEL assay showed that the number of apoptotic renal tubular epithelial cells in the SPIO-BMSC group was significantly lower than that in the PBS group. The T2 value of the renal lesion was the highest on day 1 after cell transplantation, and it gradually decreased with time in both the PBS and SPIO-BMSC groups but was always the lowest in the SPIO-BMSC group. Conclusion. SPIO-labeled BMSC transplantation can significantly promote the recovery of RIRI and noninvasive dynamic monitoring of engrafted cells and can also be performed simultaneously with MRI in vivo for the early prediction of therapeutic effects.
Ordered Quasi(BI)-Γ-Ideals in Ordered Γ-Semirings
Authors: Koam Ali N. A. , Haider Azeem , Ansari Moin A.
Published: March 2019

In this paper, we have defined ordered quasi-Γ-ideals and ordered bi-Γ-ideals in ordered Γ-semirings by defining the relation “≤” in ordered Γ semiring S as a≤b if a+x=b for any a,b,x∈S. By using this relation we have shown that ordered quasi-Γ-ideals and ordered bi-Γ-ideals in ordered Γ-semirings are generalization of quasi-ideals and bi-ideals in ordered semirings. Properties of many types of ordered Γ-ideals including (semi)prime, (strongly) irreducible, and maximal ordered quasi-Γ-ideals and ordered bi-Γ-ideals in ordered Γ-semirings S have been studied.
Experimental Studies on the Mechanical Properties of Loess Stabilized with Sodium Carboxymethyl Cellulose
Authors: Ma Hongwang , Ma Qi
Published: March 2019

This research investigated the use of sodium carboxymethyl cellulose (CMC) as a reinforcement to improve mechanical properties of loess soil found in northwestern China. The mechanical properties of loess were determined by unconfined compressive strength and split tensile strength tests. Three different contents of CMC were adopted: 0.5%, 1.0%, and 1.5%. The results showed that utilizing CMC reduced the maximum dry density of the loess. The compressive strength, tensile strength, and Young’s modulus are enough to construct low-rise buildings when the CMC content exceeds 1.0%, based on existing standards. This research thus provides a prospective sustainability method for loess stabilization.
Broad Cytotoxic Targeting of Acute Myeloid Leukemia by Polyclonal Delta One T Cells
Authors: Di Lorenzo Biagio , Simões André E. , Caiado Francisco , Tieppo Paola , Correia Daniel V. , Carvalho Tânia , da Silva Maria Gomes , Déchanet-Merville Julie , Schumacher Ton N. , Prinz Immo , Norell Haakan , Ravens Sarina , Vermijlen David , Silva-Santos Bruno
Published: March 2019

Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1+ T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of “Delta One T” (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy. Unlike chemotherapy, DOT-cell targeting did not select for outgrowth of specific AML lineages, suggesting a broad recognition domain, an outcome that was consistent with the polyclonality of the DOT-cell T-cell receptor (TCR) repertoire. However, AML reactivity was only slightly impaired upon Vδ1+ TCR antibody blockade, whereas it was strongly dependent on expression of the NKp30 ligand, B7-H6. In contrast, DOT cells did not show reactivity against normal leukocytes, including CD33+ or CD123+ myeloid cells. Adoptive transfer of DOT cells in vivo reduced AML load in the blood and target organs of multiple human AML xenograft models and significantly prolonged host survival without detectable toxicity, thus providing proof-of-concept for DOT-cell application in AML treatment.
COPD: Rethinking Patient Management – How to Approach a Challenging Patient Group Successfully
Authors: Jany Berthold H. , Bals Robert , Buhr-Schinner Heike , Dreher Michael , Koczulla A. Rembert , Jany Luitgard , Meyer Andreas , Randerath Winfried
Published: March 2019

In comparison to other chronically ill people, patients suffering from chronic obstructive pulmonary disease (COPD) have many additional difficulties to face and conquer. Due to the contribution of avoidable causes of their illness (“smokers’ lung”), society holds people with COPD responsible for their disease, which in return often leads to stigmatization and social isolation. In addition, COPD patients commonly belong to a less privileged social class, own a low socioeconomic status, and lower education. Their physical symptoms are easily observable and – by employing moderate adherence – treatable. Nonetheless, the influence of COPD on a patient’s psyche often plays an overly prominent role during therapy. “There is only half a patient laying on the examination table,” a revelation that sums up the current state of COPD research and the result of the expert meeting “Luftschlösser” (“castles in the clouds”), which took place in spring 2018. Within the limits of the meeting, participants identified practically applicable approaches aiming to enhance the patient management of this challenging patient group. These considerations are supposed to support healthcare professionals in their daily work and aim to improve the therapy as well as the outcome for COPD patients.
Combination of Resection and Ablative Treatment for Hepatocellular Carcinoma: Usefulness of Complementary Radiofrequency Ablation
Authors: Hiraoka Atsushi , Hirooka Masashi , Ochi Hironori , Koizumi Yohei , Izumoto Hirofumi , Ueki Hidetaro , Tsuruta Miho , Ono Atsushi , Yoshino Takeaki , Aibiki Toshihiko , Okudaira Tomonari , Yamago Hiroka , Suga Yoshifumi , Iwasaki Ryuichiro , Mori Kenichiro , Miyata Hideki , Kishida Masato , Tsubouchi Eiji , Abe Masanori , Matsuura Bunzo , Ninomiya Tomoyuki , Joko Kouji , Kawasaki Hideki , Hiasa Yoichi , Michitaka Kojiro
Published: March 2019

Aim/Background: In HCC patients with multiple tumors in separate segments, monotherapy with surgical resection is often difficult when the estimated residual liver volume after surgery is thought to be inadequate. We evaluated the usefulness of resection combined with low invasive radiofrequency ablation (RFA) for treatment of such cases. Materials/Methods: We analyzed 115 HCC patients with countable multiple tumors (≤5) without vascular invasion and/or extrahepatic metastasis, and treated solely with resection (SR group: n = 82), or with both resection and RFA (Comb group: n = 33) from January 2000 to December 2017. Clinical characteristics, overall survival rate (OSR), and disease-free survival rate (DFSR) were analyzed in a retrospective manner. Results: There were 88 males (76.5%) and the average age of all patients was 67.8 ± 8.9 years. The average number of tumors and average maximum tumor size were 2.4 ± 0.7 and 4.1 ± 2.1 cm, respectively. Forty-two (36.5%) patients were classified as beyond up-to-7 criteria. The 3- and 5-year OSRs in the SR group were 82.0 and 67.0%, respectively, and in the Comb group were 75.2 and 65.6%, respectively (p = 0.244), while the 3- and 5-year DFSRs in the SR group were 45.2 and 28.0%, respectively, and those in the Comb group were 37.3 and 23.3%, respectively (p = 0.257). Conclusion: The combination of surgical resection and complementary RFA may be an effective strategy for treating HCC patients with countable multiple tumors, who are otherwise difficult to treat with surgical resection or RFA alone.
Association between Primary Open-Angle Glaucoma and Cognitive Impairment as Measured by the Montreal Cognitive Assessment
Authors: McCoskey Makayla , Addis Victoria , Goodyear Kendall , Sankar Prithvi S. , Ying Gui-Shuang , Yu Yinxi , Salowe Rebecca , Cui Qi N. , Miller-Ellis Eydie , Maguire Maureen , O'Brien Joan M.
Published: March 2019

Background: It is currently unclear whether primary open-angle glaucoma (POAG) affects neurological functions outside of vision, such as cognition. Objective: This study examined the association between POAG and cognitive impairment in African Americans. Methods: Masked interviewers administered the Montreal Cognitive Assessment (MoCA) to patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study at the Scheie Eye Institute. Cases were further assessed for retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss. Univariate and multivariate linear regression analyses were performed to compare mean MoCA score between cases and controls and to assess the association between POAG severity and MoCA score. Results: A total of 137 patients completed the MoCA, including 70 cases and 67 controls. The mean age ± SD was 68.7 ± 11.2 years for cases and 65.7 ± 10.4 years for controls (p = 0.11). The mean MoCA total score (out of 30 points) was 20.3 among POAG cases and 21.3 among controls (mean difference = –1.03, 95% confidence interval, CI = –2.54 to 0.48, p = 0.18). After adjusting for age, gender, education level, diabetes, hypertension, and smoking status, the mean difference in the MoCA total score between cases and controls was –0.64 (95% CI = –1.72 to 0.45, p = 0.25). Among cases, more VF loss was associated with lower total MoCA score for mean deviation (adjusted linear trend p = 0.02) and VF index (adjusted linear trend p = 0.03). There was no significant association between average RNFL thickness and total MoCA score. Conclusions: POAG cases and controls had similar neurocognitive function as measured by the MoCA. Among POAG cases, worse VF loss was associated with lower MoCA. Future studies are needed to further elucidate the clinical effect of neuropathy in POAG.
Diagnostic A-Scan of Choroidal Melanoma: Automated Quantification of Parameters
Authors: Fonkeu Yombe , Singh Nakul , Hayden-Loreck Brandy , Singh Arun D.
Published: March 2019

Aim: To develop an automated algorithm to quantify ultrasonographic A-scan parameters of choroidal melanoma. Methods: The study included 100 consecutive patients with a clinical diagnosis of choroidal melanoma. Ultrasonographic A-scans (8 MHz, 1,550 m/s, tissue sensitivity = 67 dB) were performed by standard techniques. We created and then utilized a MATLAB® script to generate four quantifiable A-scan parameters: (1) tumor height (mm), (2) the number of internal reflectivity peaks (numerical value), (3) median internal reflectivity (%), and (4) angle κ (°). Results: There were small (≤2.5 mm, n = 32), medium (2.6–10.0 mm, n = 53), and large (> 10.0 mm, n = 14) tumors. The mean number of internal reflectivity peaks counted between the two tumor boundary spikes (surface and base) was 10.0 (σ = 8.7, range 1–37). The median value of the internal reflectivity peaks for all cases varied from 19.8 to 99.5 (mean = 68.3, σ = 20.5). A statistically significant correlation was observed between the tumor height categories and each of the three A-scan parameters: the number of internal reflectivity peaks (ρ = 0.90, p < 0.01), median internal reflectivity (ρ = –0.63, p < 0.01), and a positive angle κ (ρ = –0.32, p = 0.03). Conclusions: An automated algorithm can provide quantifiable A-scan parameters for choroidal melanoma.
Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses
Authors: Saidova Aziza , Bublin Merima , Schmidthaler Klara , Fajgelj Veronika , Klinglmueller Florian , Spittler Andreas , Hafner Christine , Szépfalusi Zsolt , Breiteneder Heimo , Eiwegger Thomas
Published: March 2019

Peanut allergy is considered to be the most common cause for food-induced anaphylaxis. Currently, no approved treatment is available. Avoidance is the only measure to prevent anaphylactic reactions to peanuts. T-helper cells are of special importance for the sensitization process and the maintenance of allergic inflammation. Identifying markers of allergen-specific T-cell responses may help to develop novel treatment approaches. Therefore, we aimed to define new T-cell target genes in Ara h 2-specific T cells and to investigate the possibility of using them as biomarkers of peanut allergy in peripheral blood mononuclear cells (PBMCs). We performed whole mRNA array analysis (whole human genome oligo microarray) of in vitro expanded Ara h 2-specific T cells (CFSElowCD3+CD4+) from 5 peanut-allergic (PA) and 5 non-peanut-sensitized individuals. Expression of selected genes as a result of a two-step bioinformatic approach was confirmed in a second cohort by quantitative PCR. TGF-β- activated kinase 1 and MAP3K7 binding protein 3 (TAB3), calcium/calmodulin-dependent protein kinase type IV (CAMK4) and HemK methyltransferase family member 1 (HEMK1) were significantly upregulated in Ara h 2-specific T cells of PA patients. In addition, the expression of these genes was also assessed in unstimulated PBMCs from a cohort (n = 43) of PA, atopic non-PA, and nonatopic controls. Interestingly, in unstimulated PBMCs, TAB3 expression was significantly downregulated in PA patients compared to atopic non-PA individuals. Thus, TAB3 may play a significant role at the level of T-cell activation and may also be a candidate biomarker for PA.