bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusion, Access, and Civility in Public Bioethics
Authors: Dresser Rebecca
Published: May 2017

I could tell many war stories about my experience serving on the President's Council on Bioethics—one of the most controversial national bioethics commissions so far—but I want to focus instead on how the experience influenced my views on bioethics, politics, and the potential contributions of national commissions. The executive order that established the Council directed it to consider policy questions, but it spoke primarily of providing a forum for national discussion, inquiry, and education. In this sense, the Council's mission departed from that of other national bioethics commissions, which have had more direct policy functions. Most bioethics commissions consider a range of ethical positions in their reports, but their primary objective has been to develop consensus recommendations on whatever topic they are addressing. The Council's executive order moved away from the consensus‐based policy model and called for deep attention to contested ideas. Although the search for consensus may be the most suitable approach for policy activities, it can lead to a bland and anemic version of bioethics. The Council sought to contribute thick bioethical analysis.
A Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations
Authors: Pacheco-Cuéllar Guillermo , Gauthier Julie , Désilets Valérie , Lachance Christian , Lemire-Girard Marlène , Rypens Françoise , Le Deist Françoise , Decaluwe Hélène , Duval Michel , Bouron-Dal Soglio Dorothée , Kokta Victor , Haddad Élie , Campeau Philippe M
Published: May 2017

Congenital disorders of glycosylation (CDGs) affect multiple systems and present a broad spectrum of clinical features, often including skeletal dysplasia. Exome sequencing has led to the identification of new CDG genes. Immune and skeletal phenotypes associated with mutations in PGM3, encoding a protein that converts N-acetyl-glucosamine-6-phosphate into N-acetyl-glucosamine-1-phosphate, were recently reported. Through exome sequencing, we identified a novel homozygous mutation (c.1135T>C; p.Phe379Leu) in PGM3 in two siblings with bone marrow failure, severe combined immunodeficiency, renal and intestinal malformations, and a skeletal dysplasia resembling Desbuquois dysplasia. Severe respiratory compromise secondary to lung hypoplasia and pulmonary hypertension, and intestinal obstruction led to their demise. We thus report the most severe phenotype described so far associated with PGM3 mutations. This CDG should be considered in the presence of skeletal dysplasia associated with severe immunodeficiency. © 2017 American Society for Bone and Mineral Research.
Retracted: Effects of shRNA‐Mediated Silencing of PKM2 Gene on Aerobic Glycolysis, Cell Migration, Cell Invasion, and Apoptosis in Colorectal Cancer Cells
Authors: Yan Xiao‐Ling , Zhang Xue‐Bin , Ao Ran , Guan Lin
Published: May 2017

This study aims to explore the effects of shRNA‐mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT‐PCR, Western blotting, and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector, and PKM2‐shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose‐6‐phosphate dehydrogenase (G‐6‐PD) coupled colorimetric assay and enzyme coupling rate method. The extracellular lactate concentration was measured by ultraviolet spectrophotometer and caspase activity was measured using spectrophotometry. The proliferation, cell cycle, apoptosis, invasion, and migration of CRC cells were detected by cell counting kit‐8 (CCK‐8) assay, flow cytometry, transwell assay, and scratch test. Three groups of nude mice were injected with 0.2 mL single‐cell suspension from the blank, vector, and PKM2‐shRNA groups, respectively. PKM2 protein content in CRC tissues was higher than that in adjacent normal tissues. Results showed that the PKM2‐shRNA group exhibited significantly lower mRNA and protein expressions of PKM2, decreased PKM2 activity, reduced lactate metabolism level, increased cell apoptosis rate, elevated caspase‐3 and caspase‐9 activity, weakened proliferation, and a reduction in cell invasion and migration ability compared to the vector and blank groups. The optical density (OD) value was lower in the PKM2‐shRNA group than in the blank and vector groups. These findings indicate that shRNA‐mediated silencing of PKM2 gene promotes apoptosis and inhibits aerobic glycolysis, proliferation, migration, and invasion in CRC cells. J. Cell. Biochem. 118: 4792–4803, 2017. © 2017 Wiley Periodicals, Inc.
Activation of MMPs in Macrophages by Mycobacterium tuberculosis via the miR‐223‐BMAL1 Signaling Pathway
Authors: Lou Jun , Wang Yongli , Zhang Zhimin , Qiu Weiqiang
Published: May 2017

An interaction between Mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on M. tuberculosis‐triggered organ lesions. In this study, we focused on the regulation of the expression of matrix metalloproteinases (MMPs), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following M. tuberculosis infection. Female BALB/c mice were intravenously injected with the M. tuberculosis strain H37Rv at 0 h zeitgeber time (ZT0) or 12 h zeitgeber time (ZT12). The expression and activity of MMP‐1, ‐2, ‐3, and ‐9 in lungs and spleens were then evaluated. In vitro, peritoneal macrophages were harvested at ZT0 or at ZT12 and infected with 10 MOI M. tuberculosis. The expression of MMPs, microRNA‐223 and BMAL1 was analyzed by qRT‐PCR and/or Western blot. The binding of BMAL1 3′‐UTR by miR‐223 was confirmed by luciferase activity assay. Additionally, wild‐type BMAL1 or NLSmut BMAL1 plasmids were transfected to evaluate the effect of BMAL1 on MMPs. The results showed a differential expression of MMPs in mice tissues infected at different times. M. tuberculosis infection caused enhanced MMP‐1, ‐9, and miR‐223 expression, with inhibited BMAL1 expression. MiR‐223 modulated BMAL1 expression via the direct binding of BMAL1 3′‐UTR. Furthermore, wild‐type BMAL1 other than NLSmut BMAL1 attenuated MMPs expression in M. tuberculosis‐infected macrophages. Overall, this study demonstrated a potential involvement of circadian rhythm in MMP activation by M. tuberculosis in macrophages. J. Cell. Biochem. 118: 4804–4812, 2017. © 2017 Wiley Periodicals, Inc.
COMMD1: A Multifunctional Regulatory Protein
Authors: Riera‐Romo Mario
Published: May 2017

The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates, and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF‐κB‐mediated transcription, hypoxia induced transcription, DNA damage response, and oncogenesis. The present work reviews the molecular mechanisms and biological processes regulated by COMMD1 that have been described so far, emphasizing in the regulatory role of the protein and its importance for cellular homeostasis. J. Cell. Biochem. 119: 34–51, 2018. © 2017 Wiley Periodicals, Inc.
CRISPR Editing in Biological and Biomedical Investigation
Authors: Ju Xing‐Da , Xu Jing , Sun Zhong Sheng
Published: May 2017

The CRISPR (clustered regularly interspaced short palindromic repeat)‐Cas (CRISPR‐associated protein) system, a prokaryotic RNA‐based adaptive immune system against viral infection, is emerging as a powerful genome editing tool in broad research areas. To further improve and expand its functionality, various CRISPR delivery strategies have been tested and optimized, and key CRISPR system components such as Cas protein have been engineered with different purposes. Benefiting from more in‐depth understanding and further development of CRISPR, versatile CRISPR‐based platforms for genome editing have been rapidly developed to advance investigations in biology and biomedicine. In biological research area, CRISPR has been widely adopted in both fundamental and applied research fields, such as genomic and epigenomic modification, genome‐wide screening, cell and animal research, agriculture transforming, livestock breeding, food manufacture, industrial biotechnology, and gene drives in disease agents control. In biomedical research area, CRISPR has also shown its extensive applicability in the establishment of animal models for genetic disorders, generation of tissue donors, implementation of antimicrobial and antiviral studies, identification and assessment of new drugs, and even treatment for clinical diseases. However, there are still several problems to consider, and the biggest concerns are the off‐target effects and ethical issues of this technology. In this prospect article, after highlighting recent development of CRISPR systems, we outline different applications and current limitations of CRISPR in biological and biomedical investigation. Finally, we provide a perspective on future development and potential risks of this multifunctional technology. J. Cell. Biochem. 119: 52–61, 2018. © 2017 Wiley Periodicals, Inc.
Vitamin D3 Alters the Expression of Toll‐like Receptors in Peripheral Blood Mononuclear Cells of Patients With Systemic Lupus Erythematosus
Authors: Yazdanpanah Esmaeil , Mahmoudi Mahmoud , Sahebari Maryam , Rezaieyazdi Zahra , Esmaeili Seyed‐Alireza , Tabasi Nafiseh , Jaberi Soheila , Sahebkar Amirhossein , Rastin Maryam
Published: May 2017

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self‐nucleic acids by intracellular Toll‐like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti‐inflammatory and immunomodulatory effects of 1,25‐dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention. The present study investigated the effects of vitamin D3 on the expression of TLR3, TLR7, and TLR9 in SLE patients. Study participants included 20 SLE patients and 20 age‐ and sex‐matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured in the presence or absence of vitamin D3 (50 nM). Then RNA was extracted, cDNA was synthesized and gene expression levels of TLR3, TLR7, and TLR9 were assessed using real‐time PCR. Up‐regulated expression levels of TLR7 and TLR9 were observed in the PBMCs of SLE patients in comparison with controls. Culturing PBMCs with vitamin D3 significantly down‐regulated the expression of TLR3 (8.86 ± 4.2 for SLE patients vs. 45.34 ± 18.6 for control; P = 0.03), TLR7 (17.91 ± 7.7 for SLE patients vs. 242.37 ± 89.6 for controls; P = 0.0001) and TLR9 (4.67 ± 1.9 for SLE patients vs. 8.9 ± 1.5 for controls; P = 0.007) in SLE patients in comparison with healthy controls. The results of the current study suggest that vitamin D3 could exert some of its immunomodulatory effects in SLE patients via affecting the expression levels of some TLRs. J. Cell. Biochem. 118: 4831–4835, 2017. © 2017 Wiley Periodicals, Inc.
High‐resolution melting analysis assay for identification of Fonsecaea species
Authors: Shi Minglan , Li Xiqing , Feng Jiao , Jia Shulin , Xiao Xing , Chen Chunmei , Fransisca Cindy , Xi Liyan , Zhang Junmin
Published: May 2017

Background

Chromoblastomycosis (CBM) is a chronic fungal disease. In China, the principle etiologic agent was a group of dematiaceous fungi, including Fonsecaea monophora, Fonsecaea nubica, and Cladophialophora carrionii. Although the Fonsecaea species have similar morphology, their pathogenicity is quite different. This study aims to establish a new solution for early identification of Fonsecaea species because of their distinctive potential infection risk.

Methods

Five reference strains and 35 clinical isolates from patients with CBM, preserved in our laboratory, were used in this study. The universal primer ITS1 and ITS2 were chosen to amplify the highly conserved regions of rDNA. High‐resolution melting (HRM) analysis was performed using the LIGHTCYCLER® 96 System. All the amplicons were verified by direct sequencing and the sequence were aligned with those in GenBank by BLAST analysis.

Results

We successfully differentiated the five strains according to their different Tm values and curve shapes. The 35 clinical isolates from patients were identified as 24 strains for F. monophora and 11 strains for F. nubica, which is consistent with the DNA sequencing results.

Conclusion

It is the first time to use HRM analysis for identification of Fonsecaea species. Since the CBM etiologic agent in South China is mainly F. monophora and F. nubica, this strategy is sufficient to be applied in the clinical examination with high accuracy, speed, and throughput.
Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients
Authors: Xia Yan , Wang Dawei , Zhang Nan , Wang Zhihao , Pang Li
Published: May 2017

Aim

To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC).

Patients and Methods

Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5‐year outcome.

Results

Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence‐free survival and overall survival.

Conclusion

Our results suggest that a high peri‐operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival.
Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling
Authors: Shears Stephen B.
Published: May 2017

Inositol pyrophosphates are small, diffusible signaling molecules that possess the most concentrated three‐dimensional array of phosphate groups in Nature; up to eight phosphates are crammed around a six‐carbon inositol ring. This review discusses the physico‐chemical properties of these unique molecules, and their mechanisms of action. Also provided is information on the enzymes that regulate the levels and hence the signaling properties of these molecules. This review pursues the idea that many of the biological effects of inositol pyrophosphates can be rationalized by their actions at the interface of cell signaling and metabolism that is essential to cellular and organismal homeostasis.
The genetic factors contributing to the development of Wilm's tumor and their clinical utility in its diagnosis and prognosis
Authors: Bahrami Afsane , Joodi Marjan , Maftooh Mina , Ferns Gordon A. , M. Ahmadi Mehrdad , Hassanian Seyed M. , Avan Amir
Published: May 2017

Mutations in the Wilm's tumor 1 (WT1) gene are associated with a wide spectrum of renal manifestations, ultimately leading to end‐stage kidney failure. There is an inadequate understanding of the molecular functions of WT1 in renal development, and this has limited the potential for therapeutic interventions in WT1‐related diseases. In this review, we discuss the existing data on the genetic and epigenetic abnormalities that have been described in WTs and their potential utility as biomarkers for risk stratification, prediction and prognosis in patients with WTs.
Humanized mice: A brief overview on their diverse applications in biomedical research
Authors: Fujiwara Shigeyoshi
Published: May 2017

Model animals naturally differ from humans in various respects and results from the former are not directly translatable to the latter. One approach to address this issue is humanized mice that are defined as mice engrafted with functional human cells or tissues. In humanized mice, we can investigate the development and function of human cells or tissues (including their products encoded by human genes) in the in vivo context of a small animal. As such, humanized mouse models have played important roles that cannot be substituted by other animal models in various areas of biomedical research. Although there are obvious limitations in humanized mice and we may need some caution in interpreting the results obtained from them, it is reasonably expected that they will be utilized in increasingly diverse areas of biomedical research, as the technology for preparing humanized mice are rapidly improved. In this review, I will describe the methodology for generating humanized mice and overview their recent applications in various disciplines including immunology, infectious diseases, drug metabolism, and neuroscience.
Association of pulse pressure with left ventricular geometry and function in elderly nonhypertensive patients with diabetes: A 3D speckle tracking echocardiography study
Authors: Wang Qingqing , Tan Kaibin , Xia Hongmei , Gao Yunhua
Published: May 2017

Purpose

The aims of this study were to investigate and compare the left ventricular (LV) geometry and function in elderly nonhypertensive type 2 diabetic patients with normal (NPP, <60 mm Hg) and with high (HPP, ≥60 mmHg) 24‐hour pulse pressure, and to explore the independent predictors of LV strain values in these patients.

Methods

A total of 76 elderly nonhypertensive type 2 diabetic patients with normal (≥55%) LV ejection fraction (LVEF) were included, 36 of whom had HPP. The control group included 40 age‐ and sex‐matched healthy volunteers with normal NPP. Conventional echocardiography and three‐dimensional speckle‐tracking echocardiography (3DSTE) were performed and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured.

Results

Significant differences in the two‐dimensional LV geometry were found among the three groups (p = 0.015), and concentric geometry was most prevalent in the diabetic patients with HPP. The diabetic patients with NPP only showed significantly lower GLS than the controls (p < 0.05). However, the diabetic patients with HPP showed significantly lower LVEF and severely lower strain values in all directions than the controls and the diabetic patients with NPP (p < 0.01or p < 0.05 or p < 0.001). Fasting plasma glucose, HPP, and body mass index were independently associated with all strain parameters in diabetic patients.

Conclusions

The combination of conventional echocardiography and 3DSTE could detect LV subclinical abnormalities in nonhypertensive type 2 diabetic patients with NPP and HPP. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:416–425, 2017
Mumps outbreak in a tribal population from the Union Territory of Dadra and Nagar Haveli, India
Authors: Tilavat Siddharth M. , Vaidya Sunil R. , Hamde Venkat S.
Published: May 2017

A cluster of parotitis cases (n = 13) were observed in a tribal population of Vansda village from the Union Territory of Dadra and Nagar Haveli, India between 20th and 22nd week of 2016. Primary information was received by the local Infectious Disease Surveillance Program team, and subsequently field investigations were carried out in the affected area. Active surveillance was conducted till twice the incubation period from onset of the last surveyed case. For the laboratory investigations, 19 serum samples were collected from 11‐suspected cases and their close contacts (n = 8). All samples were transported within 12 h on icepacks to the main laboratory at Pune. Majority of the suspected mumps cases were children except four adults. Mumps infection was confirmed in 8 of 11 suspected cases with post‐onset ranging from 28 to 43 days and none from the close contacts. Both mumps specific IgM and IgG antibodies were detected in nine cases (including one equivocal) and single contact (equivocal result). Overall, ten cases and eight contacts (including one equivocal) showed mumps specific IgG antibodies. Present investigation provides information about the characteristics of mumps outbreak in a tribal community that resides in the remote areas. In addition, introduction of mumps containing vaccine in the tribal population may have added advantages in the tribal health program.
Silver nanoparticles: Antimicrobial activity, cytotoxicity, and synergism with N‐acetyl cysteine
Authors: Hamed Selwan , Emara Mohamed , Shawky Riham M. , El‐domany Ramadan A. , Youssef Tareq
Published: May 2017

The fast progression of nanotechnology has led to novel therapeutic interventions. Antimicrobial activities of silver nanoparticles (Ag NPs) were tested against standard ATCC strains of Staphylococcus aureus (ATCC 9144), Escherichia coli (O157:H7), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 90028) in addition to 60 clinical isolates collected from cancer patients. Antimicrobial activity was tested by disk diffusion method and MIC values for Ag NPs alone and in combination with N‐acetylcysteine (NAC) against tested pathogens were determined by broth microdilution method. Ag NPs showed a robust antimicrobial activity against all tested pathogens and NAC substantially enhanced the antimicrobial activity of Ag NPs against all tested pathogens. Synergism between Ag NPs and NAC has been confirmed by checkerboard assay. The effect of Ag NPs on tested pathogens was further scrutinized by Transmission Electron Microscope (TEM) which showed disruption of cell wall in both bacteria and fungi. Ag NPs abrogated the activity of respiratory chain dehydrogenase of all tested pathogens and released muramic acid content from S. aureus in culture. The cytotoxic effect of Ag NPs alone and in combination with NAC was examined using human HepG2 cells and this revealed no cytotoxicity at MIC values of Ag NPs and interestingly, NAC reduced the cytotoxic effect of Ag NPs at concentrations higher than their MIC values. Taken together, Ag NPs have robust antimicrobial activity and NAC substantially enhances their antimicrobial activities against MDR pathogens which would provide a novel safe, effective, and inexpensive therapeutic approach to control the prevalence of MDR pathogens.
Features of Tajikistan's past and future climate
Authors: Aalto Juha , Kämäräinen Matti , Shodmonov Muzaffar , Rajabov Nasimjon , Venäläinen Ari
Published: May 2017

Tajikistan is an exceptionally vulnerable Central Asian country in the face of climate change due to its' high exposure and sensitivity to climate change combined with poor adaptation capacity. Therefore, comprehensive climate data are needed for efficient planning of mitigation and adaptation. Here, the key spatio‐temporal features of Tajikistan's climate were analysed based on historical data from 52 stations with the longest time‐series covering nearly 80 years. In addition, bias‐corrected CMIP5 climate models were used to simulate future temperature and precipitation conditions across a range of time periods and greenhouse gas emission scenarios. The results show that the mean annual temperatures have risen in Tajikistan since the 1930s, average rate of change being approximately 0.1 °C decade−1. For precipitation, only a weak signal of change could be detected. The high‐resolution (30 arc seconds) spatial analyses reveal the strong control of topography on Tajikistan's climate with such coupling leading mean annual air temperatures to vary from −13.7 °C (eastern mountain regions) to 17.3 °C (low‐altitude plains). Similarly, the mean annual precipitation vary from less than 50 mm to over 1000 mm, spring being the wettest of the seasons. The future climate simulations suggest drastic increase in air temperatures; at the end of this century the temperature multi‐model mean can be approximately 2 °C (Representative Concentration Pathways, RCP2.6) to 7 °C (RCP8.5) higher compared to 1961–1990. Precipitation scenarios indicate increase in the eastern part of the country and decrease in the west. Finally, the applied spatial uncertainty analyses stress the need for the future development of the climate station network especially in high‐elevation areas associated with complex topography. These results show the pronounced climatic variation in Tajikistan and the expected near‐ and long‐term changes in air temperature and precipitation conditions, thus forming a sound basis for future planning of national mitigation and adaptation activities.
Regulatory effect of microRNA‐34a on osteogenesis and angiogenesis in glucocorticoid‐induced osteonecrosis of the femoral head
Authors: Zha Xiaolong , Sun Bolin , Zhang Rufan , Li Chen , Yan Zuoqin , Chen Jifei
Published: May 2017

Glucocorticoid‐induced osteonecrosis of the femoral head (GIOFH) is a common and devastating orthopedic disease, and its underlying mechanism remains unclear. The aim of this study was to determine the role of microRNA‐34a (mir‐34a) in GIOFH. C57 mouse mesenchymal stem cells (mMSCs) and human umbilical vein endothelial cells (HUVECs) were cultured with dexamethasone (Dex). A total of 48 adult rats were treated with glucocorticoids, and after the onset of GIOFH, each femoral head was removed. Mir‐34a mimics, an inhibitor and over‐expressing lentivirus were used in vitro and in vivo, respectively. Real‐time PCR, immunohistochemistry, ELISA, cell proliferation assays, osteoblastic differentiation, and endothelial activity assays were employed to evaluate the effect of mir‐34a on mMSCs, osteoblasts, and vascular endothelial cells in glucocorticoid‐treated mice. We found that Dex inhibited mMSC proliferation and osteoblastic differentiation, as well as the viability and activity of endothelial cells. Dex also caused osteonecrosis and decreased new vessel formation in vivo. Mir‐34a alleviated the inhibitory effects of Dex on mMSCs and osteoblasts, while facilitating its inhibitory effects on endothelial cells. Mir‐34a is an important regulator in osteogenesis and angiogenesis, and it might be useful as a therapeutic target for GIOFH. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:417–424, 2018.
Extraction and purification of five terpenoids from olibanum by ultrahigh pressure technique and high‐speed countercurrent chromatography
Authors: Yu Jinqian , Zhao Hongwei , Wang Daijie , Song Xiangyun , Zhao Lei , Wang Xiao
Published: May 2017

Five terpenoids, including two new ones, 3,7‐dioxo‐tirucalla‐8,24‐dien‐21‐oic acid (2) and 3α‐acetoxyl‐7‐oxo‐tirucalla‐8,24‐dien‐21‐oic acid (3), and three known ones, boscartol A (1), 11‐keto‐β‐boswellic acid (4), and acetyl‐11‐keto‐boswellic acid (5), have been extracted by the ultrapressure extraction and purified by pH‐zone‐refining countercurrent chromatography and high‐speed countercurrent chromatography from olibanum. For ultrapressure extraction, the optimal condition including 200 MPa of extraction pressure, ethyl acetate of extraction solvent, 1:20 (g/mL) of solid/liquid ratio, and 2 min of extraction time were obtained. For the separation, from 1.5 g of the terpenoid extract, 220.1 mg of 4, 255.5 mg of 5, and 212.3 mg of the mixture of 1, 2, and 3 were obtained by pH‐zone‐refining countercurrent chromatography under the solvent system of chloroform/ethyl acetate/methanol/water (3:1:3:2, v/v/v/v) with aqueous ammonia and trifluoroacetic acid as retention and eluter agents. The enriched mixture (210 mg) was further separated by conventional high‐speed countercurrent chromatography with petroleum ether/ethyl acetate/methanol/water (1:0.8:1.1:0.6, v/v/v/v), yielding 30.1 mg of 1, 35.5 mg of 2, 12.3 mg of 3. The structures of these five terpenoids were elucidated by extensive spectroscopic methods.
Micellar electrokinetic capillary chromatography fingerprints combined with multivariate statistical analyses to evaluate the quality consistency and predict the fingerprint–efficacy relationship of Salviae miltiorrhizae Radix et Rhizoma (Danshen)
Authors: Zhang Yujing , Yang Lanping , Zhang Jing , Shi Min , Sun Guoxiang
Published: May 2017

Micellar electrokinetic capillary chromatography fingerprinting combined with quantification was successfully established and applied to evaluate the quality consistency of Danshen, which is a medicinal herb used to treat various diseases, especially coronary cerebrovascular diseases. A background electrolyte composed of 20 mmol/L sodium tetraborate, 90 mmol/L orthoboric acid, 25 mmol/L sodium phosphate monobasic dehydrate, and 65 mmol/L sodium dodecyl sulfate was used to separate compounds. To optimize micellar electrokinetic capillary chromatography conditions, a response surface strategy was set up for orthogonal experimental design. In fingerprint assessments, a systematic quantified fingerprint method was established for integrated quality assessment of Danshen samples from qualitative and quantitative perspectives, by which the quality of 30 samples was well differentiated. The principal component analysis coupled with quantitative determination of two components was applied to explain that the quality consistency of the medicinal herb was relatively good within one harvest season, but poor among harvest seasons for the Danshen samples. In addition, the fingerprint–efficacy relationship between the chemical fingerprints and antioxidant activities was investigated utilizing orthogonal projection to latent structures, which provided important medicinal efficacy information for quality control. This work offered an efficient, holistic, and powerful approach to evaluate the quality consistency of Danshen samples.
Contribution of Perceived Cognitive Functioning to Quality of Life in Service Members and Veterans With Posttraumatic Stress Disorder
Authors: Silverberg Noah D. , Wojtowicz Magdalena , Bui Eric , Wershba Rebecca , Zafonte Ross , Laifer Lauren M. , Simon Naomi M. , Iverson Grant L.
Published: May 2017

Perceived cognitive impairment is a core clinical feature of posttraumatic stress disorder (PTSD) and may be an important determinant of quality of life (QOL) in those who suffer from this disorder. Using a clinical data repository, we evaluated this hypothesis in a cross‐sectional sample of U.S. military service members and veterans who served after September 11, 2001, and were seeking mental health treatment at a tertiary outpatient clinic. A consecutive series of 117 patients with a clinical diagnosis of PTSD completed a battery of questionnaires at intake, including the PTSD Checklist (Weathers, Litz, Herman, Huska, & Keane, 1993), a 4‐item Cognitive Symptom subscale of the Neurobehavioral Symptom Inventory (Cicerone & Kalmar, 1995), the Depression Anxiety Stress Scale‐21 (Lovibond & Lovibond, 1995), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott, Nee, Harrison, & Blumenthal, 1993). Cognitive symptom reporting was very high, even in the subgroup without a history of traumatic brain injury. In a regression analysis, cognitive symptom severity was independently associated with QOL (β = −.204). This relationship was not explained by comorbid traumatic brain injury, but was restricted to patients with comorbid depression (β = −.278 in the subgroup with an elevated Depression Anxiety Stress Scale‐21 Depression subscale; n = 91). In conclusion, perceived cognitive impairment was common in this PTSD sample and helped to explain impairments in QOL, especially in patients with comorbid depression.
Nanostructured Semiconducting Polymer Films with Enhanced Crystallinity and Reorientation of Crystalline Domains by Electrospray Deposition
Authors: Zhao Xin‐Yan , Johnston Danvers E. , Rodriguez Johan C. , Tao Zui , Mi Bao‐Xiu , Deng Weiwei
Published: May 2017

Self‐organization of conjugated polymer such as poly(3‐hexylthiophene) (P3HT) causes directional anisotropy in the charge carrier mobility. In contrast to an edge‐on orientation formed in thin films of P3HT made by spin coating, in this study electrospray deposition rotates the orientation while producing nanopillar structures as a result of Coulombic fission and significant evaporation of solvent from the droplets. The nanostructured films are investigated by scanning electron microscopy. Due to substantial polymer–air interfaces oriented perpendicular to the substrate, P3HT molecules adopt a face‐on orientation with respect to the substrate plane that is confirmed by grazing incidence X‐ray diffraction. Additionally, enhanced crystallinity (29% increase) is confirmed by a redshift in the UV–vis absorption spectra. Because deposition by electrospray is a scalable nanomanufacturing method, these results inform the design of low‐cost device layers for large‐surface‐area applications such as light emitting diodes and photovoltaics.

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Synthesized enone fatty acids resembling metabolites from gut microbiota suppress macrophage‐mediated inflammation in adipocytes
Authors: Yang Ha‐Eun , Li Yongjia , Nishimura Akira , Jheng Huei‐Fen , Yuliana Ana , Kitano‐Ohue Ryuji , Nomura Wataru , Takahashi Nobuyuki , Kim Chu‐Sook , Yu Rina , Kitamura Nahoko , Park Si‐Bum , Kishino Shigenobu , Ogawa Jun , Kawada Teruo , Goto Tsuyoshi
Published: May 2017

Scope

Recent reports indicate that gut microbiota and their metabolites may regulate host inflammatory conditions, including the chronic inflammation of obese adipose tissues. In this study, we investigated whether specific synthesized fatty acids, identical to the metabolites generated by gut microbiota, act as anti‐inflammatory factors in obesity‐induced inflammation.

Methods and results

We first used lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophages to examine the anti‐inflammatory effect of fatty acids synthesized to resemble representative polyunsaturated fatty acid metabolites from gut microbiota. Fatty acids containing an enone structure showed the most potent anti‐inflammatory activity. Enone fatty acids also displayed anti‐inflammatory effects on macrophages cocultured with hypertrophied 3T3‐L1 or immortalized primary adipocytes; and macrophages stimulated with 3T3‐L1 adipocyte conditioned medium. Consistently, the beneficial outcome was revealed in the case of LPS‐ and obesity‐induced inflammatory cytokine stimulation in ex vivo adipose tissues. Furthermore, these fatty acids recovered the suppression of β‐adrenergic receptor‐stimulated uncoupling protein 1 expression and secretion of adiponectin in C3H10T1/2 and 3T3‐L1 adipocytes, respectively, under inflammatory conditions, suggesting that enone fatty acids can ameliorate dysfunctions of adipocytes induced by inflammation.

Conclusion

These findings indicate that synthesized enone fatty acids show potent anti‐inflammatory effects, leading to the improvement of inflammation‐induced dysfunctions in adipocytes.
Real‐time dynamic MR image reconstruction using compressed sensing and principal component analysis (CS‐PCA): Demonstration in lung tumor tracking
Authors: Dietz Bryson , Yip Eugene , Yun Jihyun , Fallone B. Gino , Wachowicz Keith
Published: May 2017

Purpose

This work presents a real‐time dynamic image reconstruction technique, which combines compressed sensing and principal component analysis (CS‐PCA), to achieve real‐time adaptive radiotherapy with the use of a linac‐magnetic resonance imaging system.

Methods

Six retrospective fully sampled dynamic data sets of patients diagnosed with non–small‐cell lung cancer were used to investigate the CS‐PCA algorithm. Using a database of fully sampled k‐space, principal components (PC's) were calculated to aid in the reconstruction of undersampled images. Missing k‐space data were calculated by projecting the current undersampled k‐space data onto the PC's to generate the corresponding PC weights. The weighted PC's were summed together, and the missing k‐space was iteratively updated. To gain insight into how the reconstruction might proceed at lower fields, 6× noise was added to the 3T data to investigate how the algorithm handles noisy data. Acceleration factors ranging from 2 to 10× were investigated using CS‐PCA and Split Bregman CS for comparison. Metrics to determine the reconstruction quality included the normalized mean square error (NMSE), as well as the dice coefficients (DC) and centroid displacement of the tumor segmentations.

Results

Our results demonstrate that CS‐PCA performed superior than CS alone. The CS‐PCA patient averaged DC for 3T and 6× noise added data remained above 0.9 for acceleration factors up to 10×. The patient averaged NMSE gradually increased with increasing acceleration; however, it remained below 0.06 up to an acceleration factor of 10× for both 3T and 6× noise added data. The CS‐PCA reconstruction speed ranged from 5 to 20 ms (Intel i7‐4710HQ CPU @ 2.5 GHz), depending on the chosen parameters.

Conclusions

A real‐time reconstruction technique was developed for adaptive radiotherapy using a Linac‐MRI system. Our CS‐PCA algorithm can achieve tumor contours with DC greater than 0.9 and NMSE less than 0.06 at acceleration factors of up to, and including, 10×. The reconstruction speed for the Split Bregman CS ranged from 200 to 260 ms, whereas the CS‐PCA reconstruction speed ranged from 5 to 20 ms implemented using nonoptimized MATLAB code.
Differentiating enhancing multiple sclerosis lesions, glioblastoma, and lymphoma with dynamic texture parameters analysis (DTPA): A feasibility study
Authors: Verma Rajeev Kumar , Wiest Roland , Locher Cäcilia , Heldner Mirjam Rachel , Schucht Phillip , Raabe Andreas , Gralla Jan , Kamm Christian Philipp , Slotboom Johannes , Kellner‐Weldon Frauke
Published: May 2017

Purpose

MR‐imaging hallmarks of glioblastoma (GB), cerebral lymphoma (CL), and demyelinating lesions are gadolinium (Gd) uptake due to blood–brain barrier disruption. Thus, initial diagnosis may be difficult based on conventional Gd‐enhanced MRI alone. Here, the added value of a dynamic texture parameter analysis (DTPA) in the differentiation between these three entities is examined. DTPA is an in‐house software tool that incorporates the analysis of quantitative texture parameters extracted from dynamic susceptibility contrast‐enhanced (DSCE) images.

Methods

Twelve patients with multiple sclerosis (MS), 15 patients with GB, and five patients with CL were included. The image analysis method focuses on the DSCE image time series during bolus passage. Three time intervals were examined: inflow, outflow, and reperfusion time interval. Texture maps were computed. From the DSCE image series, mean, difference, standard deviation, and variance texture parameters were calculated and statistically analyzed and compared between the pathologies.

Results

The texture parameters of the original DSCE image series for mean, standard deviation, and variance showed the most significant differences (P‐value between <0.00 and 0.05) between pathologies.

Further, the texture parameters related to the standard deviation or variance (both associated with tissue heterogeneity) revealed the strongest discriminations between the pathologies.

Conclusion

We conclude that dynamic perfusion texture parameters as assessed by the DTPA method allow discriminating MS, GB, and CL lesions during the first passage of contrast. DTPA used in combination with classification algorithms has the potential to find the most likely diagnosis given a postulated differential diagnosis.
Early regional cuprizone‐induced demyelination in a rat model revealed with MRI
Authors: Oakden Wendy , Bock Nicholas A. , Al‐Ebraheem Alia , Farquharson Michael J. , Stanisz Greg J.
Published: May 2017

The cuprizone model of demyelination is well established in the mouse as a tool for the study of the mechanisms of both demyelination and remyelination. It is often desirable, however, to have a larger model, such as the rat, especially for imaging‐based studies, yet initial work has failed to show demyelination in cuprizone‐fed rats. Several recent studies have demonstrated demyelination in the rat, but only in the corpus callosum. In this study, we acquired high‐resolution, three‐dimensional images of the whole brain every 2 weeks, using a T1‐weighted magnetization‐prepared rapid acquisition gradient echo imaging sequence, optimized for myelin contrast, in order to assess myelination across the entire rat brain over a period of 8 weeks on a 1% cuprizone diet. We observed a consistent pattern of demyelination, beginning in the cerebellum by 4 weeks and involving more rostral regions of the brain by 8 weeks on the cuprizone diet, with validation using Luxol fast blue histology. This imaging technique permits the effects of cuprizone‐induced demyelination to be followed longitudinally in a single animal, over the entire brain. In turn, this may facilitate the establishment of the cuprizone model of demyelination in the rat.
Increased complications of chronic erythrocytapheresis compared with manual exchange transfusions in children and adolescents with sickle cell disease
Authors: Woods Deborah , Hayashi Robert J. , Binkley Michael M. , Sparks Gianna W. , Hulbert Monica L.
Published: May 2017

Background

Children and adolescents with sickle cell disease (SCD) are at high risk of strokes and are frequently treated with red blood cell (RBC) transfusions. The goal is to suppress hemoglobin (Hb) S while minimizing transfusion‐induced iron overload. RBCs may be given via simple transfusion, manual exchange transfusion (MET), or erythrocytapheresis (aRBCX). Chronic transfusion practices vary among institutions.

Methods

This single‐institution, retrospective cohort study compares Hb S control and therapy complication rates between MET and aRBCX in a cohort of children and adolescents with SCD and stroke during a 5‐year period from 2008 through 2012. Duration and mode of transfusion therapy, achievement of Hb S suppression goal, iron burden by ferritin levels, and catheter complications were evaluated.

Results

Thirty‐seven children were included in analysis. The prevalence of catheter complications was 75% in aRBCX recipients compared with 0% in MET recipients (P < 0.001). There was no significant difference between modalities in achieving Hb S suppression or ferritin goals, but those receiving aRBCX had a greater likelihood of discontinuing chelation therapy. Among aRBCX recipients, adherence to >90% of transfusion appointments was associated with achieving Hb S suppression goals.

Conclusion

aRBCX may have increased complication risks compared with MET for chronic transfusion therapy in SCD. Risks and benefits of aRBCX and MET should be considered when selecting a chronic transfusion modality. Transfusion therapy modalities should be compared in prospective studies for stroke prevention in children with SCD.
Factor analysis of the Swedish version of the Dark Triad Dirty Dozen
Authors: Garcia Danilo , MacDonald Shane , Rapp‐Ricciardi Max
Published: May 2017

The aim of this study was to test the proposed three‐factor structure of the Swedish version of the Dark Triad Dirty Dozen measure. A confirmatory factor analysis showed mixed evidence for model fit. In contrast to expectations, men did not score significantly higher than women in Machiavellianism and narcissism. Nevertheless, men scored higher than women in psychopathy.
Influence of epoxy addition on the thermal, mechanical, and dielectrical properties of polycyanurate films
Authors: Deniz Merve , Sarıboğa Vedat , Yıldırım Saffettin , Deligöz Hüseyin
Published: May 2017

In the study, polycyanurate (PCN)/epoxy resin (ER) blends are prepared to enhance the physical properties of cyanate ester resins. The effects of curing schedule and blend composition on their thermal, mechanical, and dielectrical properties of cured PCN/epoxy blend films are examined. FTIR analysis of the cured blend films exhibits the expected cyanurate and oxazolidinone peaks in all blend compositions except the film thermally treated for 1 h in the presence of 1% phenol. TGA results show that the thermal stability decreases with epoxy content in the blend film. From SEM analyses, it is observed that all films have very dense, smooth, and bubble free surface without phase separation. For the pure PCN, the dielectric constants are found to be 3.54–5.91 in the range of 10−1–107 Hz between 20°C and 200°C. PCN/epoxy blends up to 50% epoxy resin show a good stability of dielectric constant in this frequency band for 200°C, which is close to the dielectric constant of the homopolymerized PCN. Beyond this percentage of epoxy resin, dielectric constants of PCN/epoxy blends greatly increase at low‐frequency region (0.1–103 Hz) due to the interfacial polarization governed by Maxwell–Wagner–Sillars effect. POLYM. ENG. SCI., 58:820–829, 2018. © 2017 Society of Plastics Engineers
A New Tool to Tackle the Opioid Epidemic: Description, Utility, and Results from the Maine Diversion Alert Program
Authors: Piper Brian J. , Desrosiers Clare E. , Fisher Harriet C. , McCall Kenneth L. , Nichols Stephanie D.
Published: May 2017

Study Objective

The opioid epidemic continues to impact the United States, and new strategies are needed to combat this epidemic. The objective of this study was to analyze 2015 drug arrest data from Maine's Diversion Alert (DA) program (diversionalert.org), compare arrest data between the first quarters of 2015 and 2016, and provide an analysis of the sex differences in the arrests as well as information about DA use.

Study Design

This was a population‐based descriptive study using data from the Maine DA program. The study population consisted of persons arrested for prescription, nonprescription, or illicit drugs.

Data Source

DA database.

Measurements and Main Results

The DA program addresses Maine's prescription drug abuse epidemic with innovative resources that provide access to drug arrest data for health care providers to identify and respond to patients at risk for overdose, those engaged in illegal prescription drug distribution, and those who need treatment. Drug arrest data from 2015 (2723 arrests) and the first quarter of 2016 (788 arrests) were compared and analyzed. The drugs implicated in the arrests were organized by Drug Enforcement Agency (DEA) schedule category and whether they were pharmaceuticals (synthesized and distributed by a pharmaceutical company) or nonpharmaceuticals (grown or synthesized in clandestine laboratories). Most arrests were for possession (64.5%) followed by trafficking (23.8%). Heroin was listed in more than three‐quarters (76.4%) of the Schedule I arrests, followed by marijuana (11.7%) and “bath salts” (6.3%). Cocaine and crack cocaine were implicated in almost half (46.7%) of the Schedule II arrests, followed by oxycodone (21.0%) and methamphetamine/amphetamine (15.8%). Buprenorphine was responsible for almost all (96.7%) of the Schedule III arrests. The benzodiazepines alprazolam (34.3%), clonazepam (33.8%), diazepam (11.9%), and lorazepam (8.5%) were listed in the preponderance of the Schedule IV arrests. Arrests increased in 2016 by 49.2% for heroin (p<0.01) and 170.0% for methamphetamine (p≤0.0005) relative to 2015. Arrests for trafficking increased by 42.9% (p<0.05). Males outnumbered females 2:1 in DA. Schedule IV agents accounted for only 6.8% of arrests for males versus 11.5% for females (p≤0.0001). Conversely, Schedule I agents were implicated in 33.0% of arrests for males versus only 27.3% for females (p<0.005).

Conclusion

DA is an important tool for providing timely information for health care providers regarding individuals with a history of past misuse of psychotherapeutic agents, particularly opioids and stimulants.