bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in Efficiency of the Electrocatalytic Reduction of Hydrogen Peroxide by Prussian Blue Produced from the [Fe(CN)5(mpz)]2– Complex
Authors: Monteiro Marcio C. , Toledo Kalil C. F. , Pires Bruno M. , Wick René , Bonacin Juliano A.
Published: March 2017

Hydrogen peroxide is one of the most important molecules in chemical signaling in living organisms. Because of this, its sensing is indispensable for the diagnosis of many diseases. Among the materials used for the detection and quantification of H2O2, Prussian Blue (PB) has been highlighted due to its performance. Therefore, the search for alternatives or the improvement of PB performance is a challenge. In this context, our motivation was to evaluate how the ligand N‐methylpyrazinium affects the structure and reactivity of Prussian Blue films produced from [Fe(CN)5(mpz)]2– (PB‐mpz). Based on the results, it was possible to conclude that the ligand is coordinated to the complex inside the PB framework and consequently contributes to the generation of a noncrystalline structure. The ions contained in buffer solutions can react with Prussian Blue by binding to Fe3+ and breaking the structure. In addition, a PB‐mpz film in HCl/KCl showed higher sensitivity towards H2O2 than a PB film.
Combined Kinetico‐Mechanistic and Theoretical Elucidation of the Oxidative Addition of Iodomethane to Cycloplatinated(II) Complexes: Controlling the Rate of trans/cis Isomerization
Authors: Shahsavari Hamid R. , Babadi Aghakhanpour Reza , Babaghasabha Mojgan , Golbon Haghighi Mohsen , Nabavizadeh S. Masoud , Notash Behrouz
Published: March 2017

The oxidative addition of iodomethane to cycloplatinated(II) complexes containing allyldiphenylphosphane (PPh2allyl) ligands, namely, [Pt(C^N)Me(PPh2allyl)] [1–4; C^N = deprotonated 2‐phenylpyridyne (ppy), 1; 2,2′‐bipyridine (bpy), 2; 2,2′‐bipyridine N‐oxide (O‐bpy), 3; and 7,8‐benzoquinoline (bzq), 4], occurs readily with trans stereochemistry to give the trans‐PtIV isomers 1a–4a, which then transform slowly to the cis‐PtIV isomers 1b–4b. All of the complexes were characterized by NMR spectroscopy, and the structures of 1b, 3a, and 3b were determined by single‐crystal X‐ray diffraction. Kinetic studies through UV/Vis spectroscopy suggested that the oxidative addition reaction proceeded through an SN2 reaction. The rate of the oxidative addition reaction was measured at different temperatures, and large negative ΔS≠ values consistent with the proposed mechanism were found for each reaction. This reaction was also monitored by NMR spectroscopy to determine a correct value for the rate of the trans/cis isomerization. The theoretical aspects of the mechanism for the oxidative addition reaction were also studied by density functional theory (DFT) calculations to support the claimed experimental results.
Optimal MEMS device for mobility and zeta potential measurements using DC electrophoresis
Authors: Karam Pascal R. , Dukhin Andrei , Pennathur Sumita
Published: March 2017

We have developed a novel microchannel geometry that allows us to perform simple DC electrophoresis to measure the electrophoretic mobility and zeta potential of analytes and particles. In standard capillary geometries, mobility measurements using DC fields are difficult to perform. Specifically, measurements in open capillaries require knowledge of the hard to measure and often dynamic wall surface potential. Although measurements in closed capillaries eliminate this requirement, the measurements must be performed at infinitesimally small regions of zero flow where the pressure driven‐flow completely cancels the electroosmotic flow (Komagata Planes). Furthermore, applied DC fields lead to electrode polarization, further questioning the reliability and accuracy of the measurement. In contrast, our geometry expands and moves the Komagata planes to where velocity gradients are at a minimum, and thus knowledge of the precise location of a Komagata plane is not necessary. Additionally, our microfluidic device prevents electrode polarization because of fluid recirculation around the electrodes. We fabricated our device using standard MEMS fabrication techniques and performed electrophoretic mobility measurements on 500 nm fluorescently tagged polystyrene particles at various buffer concentrations. Results are comparable to two different commercial dynamic light scattering based particle sizing instruments. We conclude with guidelines to further develop this robust electrophoretic tool that allows for facile and efficient particle characterization.
Regulatory requirements for genotoxicity assessment of plant protection product active ingredients, impurities, and metabolites
Authors: Booth Ewan D. , Rawlinson Paul J. , Maria Fagundes Priscila , Leiner Kevin A.
Published: March 2017

Active ingredients in plant protection products are subject to rigorous safety assessment during their development, including assessment of genotoxicity. Plant protection products are used for agriculture in multiple regions and for the registration of active ingredients it is necessary to satisfy the data requirements of these different regions. There are no overarching global agreements on which genotoxicity studies need to be conducted to satisfy the majority of regulatory authorities. The implementation of new OECD guidelines for the in vitro micronucleus, transgenic rodent somatic and germ cell gene mutation and in vivo comet assays, as well as the revision of a number of other OECD test guidelines has resulted in some changes to data requirements. This review describes the genotoxicity data requirements for chemical active ingredients as well as biologicals, microbials, ground water metabolites, metabolites, and impurities in a number of regions. Similarities and differences are highlighted. Environ. Mol. Mutagen. 58:325–344, 2017. © 2017 Wiley Periodicals, Inc.
How consistent are we? Interlaboratory comparison study in fathead minnows using the model estrogen 17α-ethinylestradiol to develop recommendations for environmental transcriptomics
Authors: Feswick April , Isaacs Meghan , Biales Adam , Flick Robert W. , Bencic David C. , Wang Rong-Lin , Vulpe Chris , Brown-Augustine Marianna , Loguinov Alex , Falciani Francesco , Antczak Philipp , Herbert John , Brown Lorraine , Denslow Nancy D. , Kroll Kevin J. , Lavelle Candice , Dang Viet , Escalon Lynn , Garcia-Reyero Natàlia , Martyniuk Christopher J. , Munkittrick Kelly R.
Published: March 2017

Fundamental questions remain about the application of omics in environmental risk assessments, such as the consistency of data across laboratories. The objective of the present study was to determine the congruence of transcript data across 6 independent laboratories. Male fathead minnows were exposed to a measured concentration of 15.8 ng/L 17α-ethinylestradiol (EE2) for 96 h. Livers were divided equally and sent to the participating laboratories for transcriptomic analysis using the same fathead minnow microarray. Each laboratory was free to apply bioinformatics pipelines of its choice. There were 12 491 transcripts that were identified by one or more of the laboratories as responsive to EE2. Of these, 587 transcripts (4.7%) were detected by all laboratories. Mean overlap for differentially expressed genes among laboratories was approximately 50%, which improved to approximately 59.0% using a standardized analysis pipeline. The dynamic range of fold change estimates was variable between laboratories, but ranking transcripts by their relative fold difference resulted in a positive relationship for comparisons between any 2 laboratories (mean R2 > 0.9, p < 0.001). Ten estrogen-responsive genes encompassing a fold change range from dramatic (>20-fold; e.g., vitellogenin) to subtle (∼2-fold; i.e., block of proliferation 1) were identified as differentially expressed, suggesting that laboratories can consistently identify transcripts that are known a priori to be perturbed by a chemical stressor. Thus, attention should turn toward identifying core transcriptional networks using focused arrays for specific chemicals. In addition, agreed-on bioinformatics pipelines and the ranking of genes based on fold change (as opposed to p value) should be considered in environmental risk assessment. These recommendations are expected to improve comparisons across laboratories and advance the use of omics in regulations. Environ Toxicol Chem 2017;36:2593–2601. © 2017 SETAC
Predicting herbicide mixture effects on multiple algal species using mixture toxicity models
Authors: Nagai Takashi
Published: March 2017

The validity of the application of mixture toxicity models, concentration addition and independent action, to a species sensitivity distribution (SSD) for calculation of a multisubstance potentially affected fraction was examined in laboratory experiments. Toxicity assays of herbicide mixtures using 5 species of periphytic algae were conducted. Two mixture experiments were designed: a mixture of 5 herbicides with similar modes of action and a mixture of 5 herbicides with dissimilar modes of action, corresponding to the assumptions of the concentration addition and independent action models, respectively. Experimentally obtained mixture effects on 5 algal species were converted to the fraction of affected (>50% effect on growth rate) species. The predictive ability of the concentration addition and independent action models with direct application to SSD depended on the mode of action of chemicals. That is, prediction was better for the concentration addition model than the independent action model for the mixture of herbicides with similar modes of action. In contrast, prediction was better for the independent action model than the concentration addition model for the mixture of herbicides with dissimilar modes of action. Thus, the concentration addition and independent action models could be applied to SSD in the same manner as for a single-species effect. The present study to validate the application of the concentration addition and independent action models to SSD supports the usefulness of the multisubstance potentially affected fraction as the index of ecological risk. Environ Toxicol Chem 2017;36:2624–2630. © 2017 SETAC
On stabilized space‐time FEM for anisotropic meshes: Incompressible Navier–Stokes equations and applications to blood flow in medical devices
Authors: Pauli L. , Behr M.
Published: March 2017

In complex applications, such as the analysis of hydraulic performance of blood pumps (ventricular assist devices), the Navier–Stokes equations have to be discretized on very anisotropic meshes. If stabilized finite element formulations are applied, standard definitions of the stabilization parameter are usually not appropriate to handle elements with a high aspect ratio. If, in addition, rotating objects, moving meshes, or turbulence has to be considered in the simulation, further modifications of the stabilization procedure have to be applied.

In this paper, we present stabilized space‐time finite element formulations of the incompressible Navier–Stokes equations that show very good convergence properties on complex anisotropic meshes and lead to reasonable numerical accuracy in complex flows when compared with experimental data. Copyright © 2017 John Wiley & Sons, Ltd.
Home‐based preparation approaches altered the availability of health beneficial components from carrot and blueberry
Authors: Gao Boyan , Yu Lu , Liu Jie , Wang Thomas T. Y. , Luo Yinghua , Yu Liangli (Lucy) , Zhang Huijuan , Gong Lingxiao , Wang Jing
Published: March 2017

This study investigated the effects of different home food preparation methods on availability of total phenolic contents (TPC) and radical scavenging components, as well as the selected health beneficial compounds from fresh blueberry and carrot. High performance liquid chromatography (HPLC) analysis revealed that ground carrots using blenders released significantly greater amount of β‐carotene than their chopped counterpart, and blueberry samples prepared with different commercial blenders/grinders released different levels of cyaniding‐3‐O‐glucoside and malvidin‐3‐O‐glucoside. Furthermore, microwaving was able to significantly alter the releasable amounts of cyaniding‐3‐O‐glucoside and malvidin‐3‐O‐glucoside from blueberries. In addition, carrots and blueberries processed using different blenders and chopping with or without microwaving differed in their available levels of TPC, and radical scavenging components against DPPH•, oxygen radicals and HO•, as well as their potential anti‐inflammatory activities. Taking together, these results indicated that home food preparation approaches may alter the availability of health components from carrots and blueberries. The results also suggested that the influence may depend on the fruit and vegetable type, but not the price of blenders/grinders.
Testing the “Boundaries” of boundary extension: Anticipatory scene representation across development and disorder
Authors: Spanò G. , Intraub H. , Edgin J. O.
Published: March 2017

Recent studies have suggested that Boundary Extension (BE), a scene construction error, may be linked to the function of the hippocampus. In this study, we tested BE in two groups with variations in hippocampal development and disorder: a typically developing sample ranging from preschool to adolescence and individuals with Down syndrome. We assessed BE across three different test modalities: drawing, visual recognition, and a 3D scene boundary reconstruction task. Despite confirmed fluctuations in memory function measured through a neuropsychological assessment, the results showed consistent BE in all groups across test modalities, confirming the near universal nature of BE. These results indicate that BE is an essential function driven by a complex set of processes, that occur even in the face of delayed memory development and hippocampal dysfunction in special populations.
Understanding the dynamics and contamination of an urban aquifer system using groundwater age (14C, 3H, CFCs) and chemistry
Authors: Mahlknecht Jürgen , Hernández‐Antonio Arturo , Eastoe Christopher J. , Tamez‐Meléndez Carol , Ledesma‐Ruiz Rogelio , Ramos‐Leal José A. , Ornelas‐Soto Nancy
Published: March 2017

The quality of the groundwater supplying drinking water to the Guadalajara metropolitan area has deteriorated due to both endogenic and exogenic processes. Previous studies of this complex neotectonic volcanic environment suggest that the sources of contamination here are underground fluids derived from an active volcanic center and surface wastewater derived from regional land‐use intensification. This study uses isotopic, gaseous, and chemical signatures to more comprehensively characterize this groundwater flow and its contamination paths. Groundwater is mainly recharged at the La Primavera Caldera to the west and is discharged into the Santiago River to the east. The exception to this trend is the Toluquilla area, where groundwater most likely represents rainfall originating from outside the basin limits. Evaporation affects groundwater in these areas, especially waters that have been affected by recycling below urban areas in the Atejamac area and by intensive agricultural activity in the Toluquilla area. Additionally, we present evidence that groundwater flow through alluvial sediments and tuffs in deeper wells mixes with a lower aquifer unit in basaltic‐andesitic rocks, which are in contact with hydrothermal fluids. Groundwater ages range from postbomb in the western and northwestern regions of the study area (i.e., the Atemajac aquifer unit) to Late Pleistocene in the southern and southeastern regions (i.e., the Toluquilla aquifer unit). Recently recharged water records little mixing and is located mostly in or near the La Primavera volcanic system. As groundwater undergoes gravitational flow towards discharge areas, it mixes with older water components. Chloride and sodium concentrations above natural background levels are primarily related to volcanic activity, nitrate is associated with human activities, and sulfate originates from both anthropogenic sources and water–rock interactions. Nitrate originating from land‐use activities (such as sewers, septic tanks, landfills, and agricultural fields) that is introduced into the deeper part of the groundwater system is expected to travel with the groundwater to the discharge areas because oxidizing conditions will prevent microbial reduction.

See Supplementary Information.
More for less: Analysis of the performance of avian acute oral guideline OECD 223 from empirical data
Authors: Edwards Peter J , Leopold Annegaaike , Beavers Joann B , Springer Timothy A , Chapman Peter , Maynard Samuel K , Hubbard Patrick
Published: March 2017

Since the publication of the Organisation for Economic Co-operation and Development (OECD) avian acute oral guideline, OECD 223, empirical data have become available to compare the performance of OECD 223 with statistical simulations used to validate this guideline and with empirical data for US Environmental Protection Agency Office of Chemical Safety and Pollution Prevention (USEPA OCSPP) guideline OCSPP 850.2100. Empirical studies comprised 244 for Northern bobwhite, of which 73 were dose–response tests and 171 were limit tests. Of the dose–response tests, 26 were conducted to OECD 223 (using 3–4 stages) and 33 to OCSPP 850.2100 (using the single 50-bird design). Data were collected from 5 avian testing laboratories from studies performed between 2006 and 2013. The success with which the LD50 and slope could be determined was 100% and 96% for OECD 223 (mean 26 birds per test) and 100% and 51% for OCSPP 850.2100 (mean 50 birds per test). This was consistent with the statistical simulations. Control mortality across all species and designs amounted to 0.26% (n = 2655) with only single mortalities occurring in any 1 study and <1% for any 1 species. The simulations used to validate the OECD 223 design showed that control mortality up to 1% will have no observable impact on the performance. The distribution of time to death for Northern bobwhite, zebra finch, and canary were obtained from 90, 29, and 17 studies, and mortalities appeared within 3 d for 71%, 95%, and 91% of birds tested, respectively. Integr Environ Assess Manag 2017;13:906–914. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

Empirical data for OECD 223 are consistent with OECD Validation Report 131. The LD50 and slope delivered 100% and 96% of time with 24 birds in test. No impact of low control and delayed mortality on estimates of LD50 and slope. Fifty percent fewer birds required to estimate acute toxicity with OECD 223 than with OCSPP 850.2100.
Employment status and occupational level of adult survivors of childhood cancer in Great Britain: The British childhood cancer survivor study
Authors: Frobisher Clare , Lancashire Emma R , Jenkinson Helen , Winter David L , Kelly Julie , Reulen Raoul C , Hawkins Michael M ,   On behalf of the British Childhood Cancer Survivor Study (BCCSS) Steering Group
Published: March 2017

The British Childhood Cancer Survivor Study (BCCSS) provides the first detailed investigation of employment and occupation to be undertaken in a large population‐based cohort. Previous studies have been limited by design issues such as using small numbers of survivors with specific diagnoses, and involved limited assessment of employment status and occupational level. The BCCSS includes 17,981 5‐year survivors of childhood cancer. Employment status and occupational level were ascertained by questionnaire from eligible survivors (n = 14,836). Multivariate logistic regression was used to explore factors associated with employment and occupation, and to compare survivors to their demographic peers in the general population. Employment status was available for 10,257 survivors. Gender, current age, cancer type, radiotherapy, age at diagnosis and epilepsy were consistently associated with being: employed; unable to work; in managerial or non‐manual occupations. Overall, survivors were less likely to be working than expected (OR (99% CI): 0.89 (0.81–0.98)), and this deficit was greatest for irradiated CNS neoplasm survivors (0.34 (0.28–0.41)). Compared to the general population, survivors were fivefold more likely to be unable to work due to illness/disability; the excess was 15‐fold among CNS neoplasm survivors treated with radiotherapy. Overall survivors were less likely to be in managerial occupations than expected (0.85 (0.77–0.94)). However, bone sarcoma survivors were more likely to be in these occupations than expected (1.37 (1.01–1.85)) and also similarly for non‐manual occupations (1.90 (1.37–2.62)). Survivors of retinoblastoma (1.55 (1.20–2.01)) and ‘other’ neoplasm group (1.62 (1.30–2.03)) were also more likely to be in non‐manual occupations than expected.
Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16‐driven oropharyngeal squamous cell carcinoma
Authors: Holzinger Dana , Wichmann Gunnar , Baboci Lorena , Michel Angelika , Höfler Daniela , Wiesenfarth Manuel , Schroeder Lea , Boscolo‐Rizzo Paolo , Herold‐Mende Christel , Dyckhoff Gerhard , Boehm Andreas , Del Mistro Annarosa , Bosch Franz X. , Dietz Andreas , Pawlita Michael , Waterboer Tim
Published: March 2017

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16‐driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh‐frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV‐driven in the presence of HPV16 DNA and HPV16 transformation‐specific RNA transcript patterns (E6*I, E1∧E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16‐driven. HPV16 E6 seropositivity was the best predictor of HPV16‐driven OPSCC (diagnostic accuracy 97% [95%CI 92–99%], Cohen's kappa 0.93 [95%CI 0.8–1.0]). Of the 66 HPV‐driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non‐HPV‐driven OPSCC, resulting in a sensitivity of 96% (95%CI 88–98) and a specificity of 98% (95%CI 90–100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16‐driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19–81), but was highly specific (100%, 95%CI 96–100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16‐driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16‐driven HNSCC outside the oropharynx.
Elevation of GPRC5A expression in colorectal cancer promotes tumor progression through VNN‐1 induced oxidative stress
Authors: Zhang Long , Li Liang , Gao Ganglong , Wei Gaigai , Zheng Yansen , Wang Chunmei , Gao Na , Zhao Yongliang , Deng Jiong , Chen Huaqing , Sun Jialiang , Li Dali , Zhang Xueli , Liu Mingyao
Published: March 2017

The clearance of oxidative stress compounds is critical for the protection of the organism from malignancy, but how this key physiological process is regulated is not fully understood. Here, we found that the expression of GPRC5A, a well‐characterized tumor suppressor in lung cancer, was elevated in colorectal cancer tissues in patients. In both cancer cell lines and a colitis‐associated cancer model in mice, we found that GPRC5A deficiency reduced cell proliferation and increased cell apoptosis as well as inhibited tumorigenesis in vivo. Through RNA‐Seq transcriptome analysis, we identified oxidative stress associated pathways were dysregulated. Moreover, in GPRC5A deficient cells and mouse tissues, the oxidative agents were reduced partially due to increased glutathione (GSH) level. Mechanistically, GPRC5A regulates NF‐κB mediated Vanin‐1 expression which is the predominant enzyme for cysteamine generation. Administration of cystamine (the disulfide form of cysteamine) in GPRC5A deficient cell lines inhibited γ‐GCS activity, leading to reduction of GSH level and increase of cell growth. Taken together, our studies suggest that GPRC5a is a potential biomarker for colon cancer and promotes tumorigenesis through stimulation of Vanin‐1 expression and oxidative stress in colitis associated cancer. This study revealed an unexpected oncogenic role of GPRC5A in colorectal cancer suggesting there are complicated functional and molecular mechanism differences of this gene in distinct tissues.
Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics
Authors: Nielson Carrie M , Wiedrick Jack , Shen Jian , Jacobs Jon , Baker Erin S , Baraff Aaron , Piehowski Paul , Lee Christine G , Baratt Arie , Petyuk Vladislav , McWeeney Shannon , Lim Jeong Youn , Bauer Douglas C , Lane Nancy E , Cawthon Peggy M , Smith Richard D , Lapidus Jodi , Orwoll Eric S ,   for the Osteoporotic Fractures in Men (MrOS) Study Research Group
Published: March 2017

Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2, n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, –0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (eg, CD14 and SHBG), whereas others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction. © 2017 American Society for Bone and Mineral Research.
Applied Induced Pluripotent Stem Cells in Combination With Biomaterials in Bone Tissue Engineering
Authors: Ardeshirylajimi Abdolreza
Published: March 2017

Due to increasing of the orthopedic lesions and fractures in the world and limitation of current treatment methods, researchers, and surgeons paid attention to the new treatment ways especially to tissue engineering and regenerative medicine. Innovation in stem cells and biomaterials accelerate during the last decade as two main important parts of the tissue engineering. Recently, induced pluripotent stem cells (iPSCs) introduced as cells with highly proliferation and differentiation potentials that hold great promising features for used in tissue engineering and regenerative medicine. As another main part of tissue engineering, synthetic, and natural polymers have been shown daily grow up in number to increase and improve the grade of biopolymers that could be used as scaffold with or without stem cells for implantation. One of the developed areas of tissue engineering is bone tissue engineering; the aim of this review is present studies were done in the field of bone tissue engineering while used iPSCs in combination with natural and synthetic biomaterials. J. Cell. Biochem. 118: 3034–3042, 2017. © 2017 Wiley Periodicals, Inc.
When Emotional Pain Becomes Physical: Adverse Childhood Experiences, Pain, and the Role of Mood and Anxiety Disorders
Authors: Sachs‐Ericsson Natalie J. , Sheffler Julia L. , Stanley Ian H. , Piazza Jennifer R. , Preacher Kristopher J.
Published: March 2017

Objective

We examined the association between retrospective reports of adverse childhood experiences (ACEs) and painful medical conditions. We also examined the mediating and moderating roles of mood and anxiety disorders in the ACEs–painful medical conditions relationship.

Method

Ten‐year longitudinal data were obtained from the National Comorbidity Surveys (NCS‐1, NCS‐2;N= 5001). The NCS‐1 obtained reports of ACEs, current health conditions, current pain severity, and mood and anxiety disorders. The NCS‐2 assessed for painful medical conditions (e.g., arthritis/rheumatism, chronic back/neck problems, severe headaches, other chronic pain).

Results

Specific ACEs (e.g., verbal and sexual abuse, parental psychopathology, and early parental loss) were associated with the painful medical conditions. Baseline measures of depression, bipolar disorder, and posttraumatic stress disorder were also associated with the number of painful medical conditions. Anxiety and mood disorders were found to partially mediate the ACEs–painful medical conditions relationship. We determined through mediation analyses that ACEs were linked to an increase in anxiety and mood disorders, which, in turn, were associated with an increase in the number of painful medical conditions. We determined through moderation analyses that ACEs had an effect on increasing the painful medical conditions at both high and low levels of anxiety and mood disorders; though, surprisingly, the effect was greater among participants at lower levels of mood and anxiety disorders.

Conclusion

There are pernicious effects of ACEs across mental and physical domains. Dysregulation of the hypothalamic‐pituitary‐adrenal stress response and the theory of reserve capacity are reviewed to integrate our findings of the complex relationships.
Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis
Authors: Tournadre Anne , Pereira Bruno , Dutheil Fréderic , Giraud Charlotte , Courteix Daniel , Sapin Vincent , Frayssac Thomas , Mathieu Sylvain , Malochet‐Guinamand Sandrine , Soubrier Martin
Published: March 2017

Background

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti‐interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA.

Methods

Twenty‐one active RA patients treated with TCZ were included in a 1 year open follow‐up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual‐energy X‐ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non‐RA controls matched for age, sex, body mass index, and metabolic syndrome.

Results

Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut‐off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed.

Conclusions

Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat distribution was observed. In contrast, muscle gain suggests that blocking IL‐6 might be efficient in treating sarcopaenia associated with RA.
Chlamydia trachomatis and HPV co‐infections in HIV negative men from a multi‐ethnic area of Northern Italy at high prevalence of cervical malignancies
Authors: Comar Manola , Monasta Lorenzo , Seraceni Silva , Colli Claudia , Luska Viviana , Morassut Sara , Clemente Libera , Drabeni Marina , Moise Gianmichele , Fontana Francesco , Suligoi Barbara
Published: March 2017

Chlamydia trachomatis and HPV coinfections in the male population are often a disregarded issue. We performed a study to evaluate the prevalence of such infections in heterosexual HIV negative men from a Northern Italy multi‐ethnic area at high prevalence for cervical malignancies. Urethral swabs (US) or first‐voided urine were evaluated retrospectively from 1317 patients attending Sexually Transmitted Infections (STI) clinic and from 3388 outpatients attending private clinics. Informations about participants’ demographic characteristics and attributes of C. trachomatis, including chronic infection, and HPV genotypes testing, were collected. Exact Fisher test, bivariate, and multivariate logistic regressions were carried out. The prevalence of C. trachomatis was 1.7% in the outpatients and 16.9% in the STI group (P < 0.0001) in which the highest frequency was observed in men of age ≤25 years. Among patients with C. trachomatis, asymptomatic HPV co‐infection was detected in 33% of men from the STI clinic and in 2% of the outpatients. Out of all coinfections, 56% were due to single HPV, with a prevalence of 73% in young STI men. The distribution of HPV genotypes confirmed the increased circulation of LR‐HPV42, HR‐HPV51, HR‐HPV52 and prHR‐HPV82, and the decreasing of HR‐HPV16. African nationalities and leucorrhea were significantly associated risk factors, while the regular condom use offered an effective protection. This study highlights the high prevalence of C. trachomatis and HPV asymptomatic co‐infection in young HIV negative men attending the STI clinic, representing a reservoir of new HPV genotypes with potential oncogenic risk.
Energy metabolism in the rat cortex under thiopental anaesthesia measured In Vivo by 13C MRS
Authors: Sonnay Sarah , Duarte João M. N. , Just Nathalie , Gruetter Rolf
Published: March 2017

Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing 13C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0.02 µmol/g/min, and the rate of the glutamate‐glutamine cycle was 0.09 ± 0.02 µmol/g/min. In astrocytes, the TCA cycle rate was 0.16 ± 0.02 µmol/g/min, accounting for a quarter of whole brain glucose oxidation, pyruvate carboxylase rate was 0.02 ± 0.01 µmol/g/min, and glutamine synthetase was 0.12 ± 0.01 µmol/g/min. Relative to previous experiments under light α‐chloralose anaesthesia, thiopental reduced oxidative metabolism in neurons and even more so in astrocytes. Interestingly, total oxidative metabolism in the cortex under thiopental anaesthesia surpassed the rate of pyruvate production by glycolysis, indicating substantial utilisation of substrates other than glucose, likely plasma lactate. © 2017 Wiley Periodicals, Inc.
The involvement of thrombin in the pathogenesis of glioblastoma
Authors: Krenzlin Harald , Lorenz Viola , Alessandri Beat
Published: March 2017

Prothrombin and its active derivative thrombin are key members of the coagulation system. The only site of extra‐hepatic thrombin expression is the central nervous system (CNS), where it is involved in brain development, protection, and regeneration. Thrombin affects various degenerative and ischemic CNS diseases like Alzheimer's, multiple sclerosis, cerebral ischemia, and hemorrhage in a dose dependent manner. Additionally, the association of thrombin with various malignancies has recently become evident. Thrombin facilitates the interaction between tumor cells with platelets, endothelial cells, and the adhesion to matrix proteins in various tumor types. Consequently, thrombin enables tumor cell seeding and metastasis, resulting in increased tumor cell growth and angiogenesis. Despite the exceptional position of thrombin in the CNS, its involvement in brain tumor course and development has so far been largely neglected. Over the last decade, several studies found a detrimental effect of thrombin in the most devastating of all primary brain tumors, glioblastomas (GBM). This review highlights the current knowledge on the involvement of thrombin in the pathophysiology and clinical course of GBMs. © 2017 Wiley Periodicals, Inc.
The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes
Authors: Hohnholt Michaela C. , Blumrich* Eva‐Maria , Waagepetersen Helle S. , Dringen Ralf
Published: March 2017

Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood‐brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U‐13C]glucose. The presence of metformin did not compromise the viability of cultured astrocytes during 4 hr of incubation, but almost doubled cellular glucose consumption and lactate release. Compared with control cells, the presence of metformin dramatically lowered the molecular 13C carbon labeling (MCL) of the cellular TCA cycle intermediates citrate, α‐ketoglutarate, succinate, fumarate, and malate, as well as the MCL of the TCA cycle intermediate‐derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA cycling ratio in metformin‐treated astrocytes. Finally, the oxygen consumption of mitochondria isolated from metformin‐treated astrocytes was drastically reduced in the presence of complex I substrates, but not of complex II substrates. These data demonstrate that exposure to metformin strongly impairs complex I–mediated mitochondrial respiration in astrocytes, which is likely to cause the observed decrease in labeling of mitochondrial TCA cycle intermediates and the stimulation of glycolytic lactate production. © 2017 Wiley Periodicals, Inc.
Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: an observational, prospective, cohort study
Authors: Perera Dhineli Michelle Patricia , Coombes Judith Ann , Shanika Lelwala Guruge Thushani , Dawson Andrew , Lynch Catherine , Mohamed Fahim , De Silva Hithanadura Asita , Jayamanne Shaluka Francis , Peters Nimali Buddhima , Myers Brooke , Coombes Ian David
Published: March 2017

Background

Quality use of medicines (QUM) has been identified as a priority in Sri Lanka.

Aim

To identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital.

Methods

An observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre‐admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre‐ and post‐admission medication regimens were recorded. Drug‐related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital.

Results

The 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge.

Conclusion

Significant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospital‐based healthcare system in Sri Lanka.
Does the Vulnerability Paradox in PTSD Apply to Women and Men? An Exploratory Study
Authors: Dückers Michel L.A. , Olff Miranda
Published: March 2017

Recent research suggests that greater country vulnerability is associated with a decreased, rather than increased, risk of mental health problems. Because societal parameters may have gender‐specific implications, our objective was to explore whether the “vulnerability paradox” equally applies to women and men. Lifetime posttraumatic stress disorder (PTSD) prevalence data for women and men were retrieved from 11 population studies (N = 57,031): conducted in Australia, Brazil, Canada, France, Lebanon, Mexico, Netherlands, Portugal, Sweden, Switzerland, and the United States. We tested statistical models with vulnerability, gender, and their interaction as predictors. The average lifetime PTSD prevalence in women was at least twice as high as it was in men and the vulnerability paradox existed in the prevalence data for women and men (R2 = .70). We could not confirm the possibility that gender effects are modified by socioeconomic and cultural country characteristics. Issues of methodology, language, and cultural validity complicate international comparisons. Nevertheless, this international sample points at a parallel paradox: The vulnerability paradox was confirmed for both women and men. The absence of a significant interaction between gender and country vulnerability implies that possible explanations for the paradox at the country‐level do not necessarily require gender‐driven distinction.
Biometric Differentiation of Wild Philippine Pigs from Introduced Sus scrofa in Modern and Archaeological Assemblages
Authors: Ingicco T. , Piper P. J. , Amano N. , Paz V. J. , Pawlik A. F.
Published: March 2017

In many parts of Eurasia, the Middle East and Southeast Asia where native wild suids occur, it is notoriously difficult to differentiate these from introduced domestic pigs in the prehistoric archaeological record. Yet, correct identification of the initial appearance or introduction of domestic pigs (Sus scrofa) is essential for determining the timing for the transition from purely hunting to the adoption of managed animal populations within different regions across the globe. In a recent review of techniques used by zooarchaeologists to distinguish between domestic and wild pig populations, the analysts concluded that the most reliable method was metrical analyses, when the data produce a clear two‐population pattern, one domestic, the other wild. In this study, we demonstrate how linear metrics are an effective tool, albeit at different levels of confidence, for differentiating the native and endemic species of Philippine pig from S. scrofa, both within modern contemporary assemblages, and the archaeological record. Copyright © 2017 John Wiley & Sons, Ltd.
Taphonomy and Paleoichnology of Olduvai Hominid 1 (OH1), Tanzania
Authors: Matu M. , Crevecoeur I. , Huchet J.‐B.
Published: March 2017

This paper presents a case study of the Late Pleistocene skeletal remains of Olduvai Hominid 1, which were unearthed in Tanzania. Excavated in 1913, this fossil shows severe damage due to subterranean termites (Insecta: Isoptera). By combining methods to quantify and locate traces on the skeleton with the study of the different taphonomic processes that altered the deposit, we demonstrate a non‐arbitrary pattern of termite alteration of the skeletal remains. These results shed new light on the possibility to reconstruct the original position of a skeleton in a deposit and the potential to infer the space of decomposition and past funerary practices. Copyright © 2017 John Wiley & Sons, Ltd.
Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients
Authors: Genvigir Fabiana D. V. , Nishikawa Alvaro M. , Felipe Claudia R. , Tedesco‐Silva Helio , Oliveira Nagilla , Salazar Antony B. C. , Medina‐Pestana Jose O. , Doi Sonia Q. , Hirata Mario H. , Hirata Rosario D. C.
Published: March 2017

Study Objective

To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose‐adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients.

Design

Pharmacogenetic analysis of patients enrolled in a previously published study.

Patients

One hundred forty‐eight adult kidney transplant recipients treated with tacrolimus, enteric‐coated mycophenolate sodium, and prednisone for 90 days posttransplantation.

Measurements and Main Results

ABCC2 c.−24C>T and c.3972C>T, ABCG2 c.421C>A, CYP2C8*3, CYP2J2 c.−76G>T, and UGT2B7 c.372A>G SNPs were determined by real‐time polymerase chain reaction. The CYP3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP3A5‐nonexpressing patients (CYP3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy‐confirmed acute rejection or delayed graft function. The CYP2J2 c.−76T allele was associated with increased risk for treatment‐induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49‐18.79, p<0.05).

Conclusion

The ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.−76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium.