bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory of Mind Deficits and Their Influence on Functional Impairment in Remitted Phase of Bipolar Disorder
Authors: Palaniappan Pradeep , Easwaran Krishnapriya
Published: August 2020

Background:

Functional impairment has been convincingly established in the euthymic/ remitted phase of bipolar disorder (BD). Though deficits in social cognition, especially theory of mind (ToM), predict functional impairment, the association has not been consistently proven.

Methods:

Thirty remitted subjects with BD (as per DSM 5) and 30 age- and gender-matched healthy controls were screened for eligibility and the sociodemographic details and ToM scores, that is, first-order ToM, second-order ToM, and Faux pas, were collected. In subjects with BD, functioning was assessed using Functioning Assessment Short Test (FAST) and illness variables were collected.

Results:

No significant difference was found in occupation or education between the groups. Remitted subjects with BD had statistically significant deficits in all domains of ToM, that is, first-order ToM ( r = 0.65), second-order ToM ( r = 0.69), and Faux pas ( r = 0.75). Significant correlations existed between first-order ToM and FAST total score, as well as second-order ToM and FAST total score, but the correlations dropped after controlling for duration of illness and number of depressive episodes. Quantile regression analysis showed that the only factors which predicted global functional impairment was a higher number of episodes ( βτ= –0.45, SE = 3.51, t = 0.13, P = 0.04), while all other illness variables and ToM failed to predict the global functioning.

Conclusion:

Though there seems to be an association between ToM and functioning, only illness variables predicted functional impairment in subjects with BD. We need prospective studies to delineate the contributors to functional impairment.
Intimate Partner Violence, Lifetime Victimization, and Sociodemographic and Clinical Profile of Women with Psychiatric Illness at a Tertiary Care Psychiatric Hospital in India
Authors: Narasimha Vranda Mysore , Naveen Kumar Channaveerachari , Muralidhar Dalibonia , Janardhana Navaneetham , Thangaraju Sivakumar Palanimuthu
Published: August 2020

Background:

Intimate partner violence (IPV) is one of the major public health problems. Little is known about the extent of violence experienced, its severity, or history of childhood abuse or exposure to intergenerational family violence in women with mental illness.

Methods:

One hundred women seeking in-patients (IP) or out-patients (OP) services at a tertiary care psychiatric setting were recruited using consecutive sampling. IPV Questionnaire and Danger Assessment Questionnaire were administered.

Results:

The data revealed a moderate level of IPV experienced by the women. In their childhood, more than one-third had undergone physical abuse by their fathers and witnessed violence by fathers toward mothers.

Conclusion:

Screening for intimate violence is essential in women attending mental health settings.
Severity Classification of Surgical Procedures and Application of Health Monitoring Strategies in Animal Research Proposals: A Retrospective Review
Authors: Herrmann Kathrin , Flecknell Paul
Published: August 2020

Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon the animals used. In an effort to reduce these harms, research on refinement has increased significantly over the past 20 years. However, the extent to which these efforts have helped to reduce the severity of the research procedures, and thus animal suffering, is uncertain. To provide an indication of the awareness and implementation of refinement methods, we reviewed the experimental techniques for 684 surgical interventions described in 506 animal research applications that had been sent to the German competent authorities for approval in 2010. In this paper, we describe and discuss the severity categorisation of the proposed surgeries and the planned health monitoring strategies. We found that the researchers frequently underestimated the levels of pain, suffering, distress and lasting harm that were to be inflicted on the animals. Furthermore, the planned health monitoring strategies were generally flawed. To ensure responsible treatment of animals and high-quality science, adequate training of research workers in recognising and alleviating animal suffering is essential.
Structure-activity Relationships for Unsaturated Dialdehydes. V. Estimation of the Lipophilicity of Nineteen Sesquiterpenoid Unsaturated Dialdehydes, and Determination of their Chemical Stability in Three In Vitro Assay Media
Authors: Sterner Olov , Andersson Marianne , Forsby Anna , Morales Paloma
Published: August 2020

The lipophilicity, expressed as log P, has been estimated for 19 sesquiterpenoid unsaturated dialdehydes by the determination of the 1-octanol/water partition coefficient for 12 of the compounds, and the reversed-phase HPLC retention data for all the compounds. The log P values obtained varied between 0.5 and 3.02. The stability of 17 unsaturated dialdehydes in three common in vitro assay media at 37°C was investigated by HPLC analysis of samples dissolved in the media. All compounds investigated were essentially stable for up to 24 hours in a phosphate buffered saline, while several of them disappeared rapidly in media containing amino acids and fetal calf serum. This chemical instability must be considered when results from biological assays of unsaturated dialdehydes are compared.
A Method Based on the Roller Chamber Technique for Determination of CO2 Production in Cultured Cells: Effects of Acrylamide in Neuroblastoma N1E115 Cultures
Authors: Nyberg Elisabet , Ekblad-Sekund Gun , Walum Erik
Published: August 2020

The effects of acrylamide on CO2 production from [14C]-labelled glucose, pyruvate and glutamine have been studied in a mouse neuroblastoma cell line C1300, clone N1E115. A rotation metabolism chamber, permitting closed incubation of monolayer, anchorage-dependent cell cultures under good physiological conditions, was developed for making the determinations. The cells were exposed to acrylamide (0.35mM) for 14 days. The total amunt of CO2 produced from glucose and pyruvate was increased by exposure to acrylamide, whereas a slight inhibition was found in the production from glutamine. The production of lactate remained unchanged. Comparison of these results with other data obtained in our laboratory leads us to conclude that the method described is relevant for the determination of energy metabolic processes through the quantification of CO2 production. Furthermore, we assume that acrylamide causes an increased demand for energy in the cells and that this demand is met by the cells through the increased oxidative phosphorylation of glucose.
The Use of Computers to Reduce Animal Experimentation in Pharmacology
Authors: Hughes Ian E.
Published: August 2020

Computers are now used routinely as tools in pharmacology, particularly in the areas of teaching, data processing and collection, information retrieval and literature searching, and in molecular modelling and drug design. Their use in these areas has enhanced research activity and has extended and increased the availability of new teaching methods. Here, their impact on the use of animals in both teaching and research is discussed. It is concluded that computers may have some potential to reduce animal experimentation in the medium to long term, but their current use as alternatives to animals has made only a marginal impact on the total number of animals utilised for experimental purposes.
Progress toward the Validation of Alternative Tests
Authors: Balls Michael , Fentem Julia H.
Published: August 2020

ECVAM's role in the practical validation of replacement alternative methods for use in regulatory testing is reviewed, including an outline of the criteria which have been used in determining ECVAM's priorities. Some of the difficulties which have arisen in validation studies are discussed, and solutions to these are proposed, with particular emphasis on ensuring that methods are sufficiently well-developed to enter the validation process, and on the ECVAM prevalidation scheme for encouraging protocol optimisation and the prior assessment of interlaboratory transferability. Comments are made on problems encountered in selecting test materials backed by adequate in vivo data and in undertaking appropriate in vivo/in vitro comparisons.
Studies on α-Hexachlorocyclohexane Cytotoxicity, Genotoxicity and Cytochrome P450 Induction in Primary Hepatocytes and Hepatoma Cell Lines from Rodents and Humans
Authors: Ferro Margherita , Bassi Anna Maria , Adamo Daniela , Mattioli Francesca , Robbiano Luigi , Nanni Giorgio
Published: August 2020

α-Hexachlorocyclohexane (α-HCH) was examined for cytotoxicity, genotoxicity and cytochrome P450 induction in primary cultures of mouse, rat and human hepatocytes and in three hepatoma cell lines (Hepa 1c1c7, FaO and Hep G2, from mouse, rat and man, respectively). The cell lines were much more sensitive to the cytotoxicity of the classical inducers phenobarbital and 3-methylcholanthrene than that of α-HCH, whereas no cytotoxicity was observed in primary hepatocytes. Exposure for 24 hours to 0.32mM α-HCH produced a modest, but statistically significant, frequency of DNA breaks, as measured by the alkaline elution assay, in the mouse Hepa 1c1c7 cell line, and the human Hep G2 cell line, but not in the rat FaO cell line. In the Hep G2 cell line, the amount of DNA fragmentation was found to increase with the length of exposure. Compared with the results of previous observations on primary cultures, with regard to species specificity, only the human cell line gave a concordant positive response. Monooxygenase activity induction in primary hepatocytes, despite rather high initial levels of 7-ethoxycoumarin-O-deethylase activity, was low with the classical inducers phenobarbital and 3-methylcholanthrene. α-HCH caused no induction of monooxygenase. The rat FaO and human Hep G2 cell lines were sensitive to α-HCH, but only after long exposure. The results of this study support the hypothesis that α-HCH might act as a weak genotoxic agent in humans, but they also suggest caution in the extrapolation to the in vivo situation of the observations made in established cell lines.
In Vitro Culture of Human Thyroid Cells: Preliminary Findings on the Role of the Pathological Condition of the Donors
Authors: Mattioli Francesca , Angiola Marianna , Fazzuoli Laura , Razzetta Francesco , Martelli Antonietta
Published: August 2020

Although primary cultures of human thyroid cells are used for endocrinological and toxicological studies, until now no attention has been paid toward verifying whether the hormonal conditions to which the gland was exposed in vivo prior to surgery could influence in vitro responses. Our findings suggest that the hormonal situation in vivo cannot be used as a predictive indicator of triiodothyronine and thyroxine release and/or S-phase frequency in vitro, either with or without the addition of bovine thyrotropin.
Interleukin-1α and Interleukin-8 Release by Human Keratinocyte Cell Culture Treated with Surfactants
Authors: Shibata Michio , Tsuda Takanari , Itagaki Hiroshi , Kato Shinobu , Kobayashi Toshiaki , Ichikawa Hideyuki , Morikawa Yoshihiro
Published: August 2020

The effects of four cosmetic surfactants on interleukin (IL)-1α and IL-8 release from human keratinocytes were studied to investigate the feasibility of using these effects for the prediction of the irritation potential of chemicals. After exposure of cells to surfactants, the amounts of IL-1α and IL-8 released into culture medium were measured by ELISA. Cytotoxicity was evaluated by using the neutral red uptake (NRU) cytotoxicity assay. Cytokine release was increased 7–15 times by sodium lauryl sulphate (SLS), laurtrimonium chloride, cocamidopropyl betaine (CPB) and Oleth-5 at cytotoxic concentrations. IL-8 release was increased 3–4 times by SLS, CPB and Oleth-5 at subcytotoxic concentrations. After exposure to SLS, IL-1α was released within 1 hour, suggesting that IL-1α release is associated with membrane damage, whereas IL-8 release continued for 24 hours, suggesting that IL-8 was produced within the cells. Cytotoxicity tests and IL-8 release assays were also performed on seven other surfactants. The results show that moderate irritants CPB and PEG-4 dioleate, which have weak cytotoxic effects, significantly increased IL-8 release from human keratinocytes. It is suggested that measurement of IL-8 release is useful for predicting the irritation potential of chemicals which cannot be detected by using the NRU cytotoxicity assay.
An Ultrastructural Evaluation of the SKIN2™ ZK1200 System as an in Vitro Model of the Human Oral Mucosa
Authors: Arenholt-Bindslev Dorthe , Torpet Lis Andersen , Josephsen Kaj
Published: August 2020

At present, there are no validated experimental models for the preclinical oral mucosa irritancy screening of dental materials and oral hygiene products. Standardised in vitro models for the assessment of skin irritancy have been marketed, and have made possible the application of such models in preclinical skin irritancy testing. Some of these are currently undergoing international interlaboratory validation. The aim of the present study was to evaluate the histology of the commercially available SKIN2™ ZK1200 system as a potential in vitro model of the human oral mucosa. Histological evaluation by light microscopy and transmission electron microscopy over 6 days revealed a fibroblast-rich matrix covered by an 8–12 cell layer of stratifying epithelium, which shared a number of basic characteristics with non-keratinised human oral mucosa (for example, desmosomes, dispersed tonofilaments, glycogen deposits, membrane-coating granules, and keratohyalin granules, both the spherical and ribosome-associated types). Exposure to a methacrylate-based dental fissure sealant for 24 hours caused structural changes in the epithelium which were not reflected by a cytochemical cytotoxicity assay (MTT).
5’-Nucleotidase Activity and Galactolipid Accumulation in Triethyllead-exposed Glial Cell Cultures
Authors: Grundt Inger K. , Rise Marvelyn , Nyland Harald
Published: August 2020

The developing nervous system is vulnerable to heavy metal exposure, which can cause alterations in neuronal and glial cells in the brain. Thus, heavy metals such as mercury and lead reduce myelin galactocerebroside (GalC) synthesis, and increase the ratio of non-hydroxylated fatty acids to hydroxylated fatty acids (GalC-N:GalC-OH) in the GalC molecules in newborn rats. This study investigated the effect of lead on the expression of myelin components by the myelin-forming oligodendroglial cells (OG) in vitro. Primary cultures of mixed glial cells from brains of newborn rats were continuously exposed to triethyllead (TEL; 1nM, 10nM, 50nM and 100nM) for 3 weeks, one week after seeding. The first morphological alteration observed was an increased proliferation of OG in cultures exposed to 10nM TEL. Biochemical analyses showed up-regulation of the enzymes, 2'3’-cyclic nucleotide 3’-phosphodiesterase and 5’-nucleotidase. GalC synthesis was also stimulated, and the ratio GalC-N:GalC-OH was reduced. The results indicate that TEL stimulates the differentiation and maturation of OG in cultures, which suggests that the alterations induced by heavy metals in newborn rats are not due to interference with the OG maturation.
Neurotoxicity of Seven MEIC Chemicals Evaluated in Organotypic Cultures of Chick Embryonic Dorsal Root Ganglia
Authors: Mandys Václav , Jirsová Katerina , Vrana Jirí
Published: August 2020

The neurotoxic effects of seven selected Multicenter Evaluation of In Vitro Cytotoxicity programme chemicals (methanol, ethanol, isopropanol, sodium chloride, potassium chloride, iron [II] sulphate and chloroform) were evaluated in organotypic cultures of chick embryonic dorsal root ganglia (DRG), maintained in a soft agar culture medium. Two growth parameters of neurite outgrowth from the ganglia — the mean radial length of neurites and the area of neurite outgrowth — were used to evaluate the toxicities of the chemicals. Dose-dependent decreases of both parameters were observed in all experiments. IC50 values (the concentration causing 50% inhibition of growth) were calculated from the dose-response curves established at three time-points during culture, i.e. 24, 48 and 72 hours. The lowest toxic effect was observed in cultures exposed to methanol (the IC50 ranging from 580mM to 1020mM). The highest toxic effect was observed in cultures exposed to iron (II) sulphate (the IC50 ranging from 1.2mM to 1.7mM). The results of other recent experiments suggest that organotypic cultures of DRG can be used during in vitro studies on target organ toxicity within the peripheral nervous system. Moreover, these cultures preserve the internal organisation of the tissue, maintain intercellular contacts, and thus reflect the in vitro situation, more precisely than other cell cultures.
Genotoxicity Screening of Leachates from Solid Industrial Wastes Evaluated with the Allium Test
Authors: Odeigah Peter G. , Ijimakinwa Jide , Lawal Bimbo , Oyeniyi Rebecca
Published: August 2020

Six solid wastes from the metal industry, from the chemical industry and from the production of pesticides were investigated for their toxic and genotoxic properties by using the Allium test. To simulate environmental conditions and better assess their environmental impact, the solid wastes were leached with water, and the water-extractable micropollutants were lyophilised before screening. The mean root lengths of onions exposed to different concentrations of the leachates were measured, and EC50 values were determined from the growth curves. The EC50 values of the wastes were ranked, in the order: organochlorine pesticide waste, settling tank sludge from a chemical company, paint sludge, lead slag, steel slag and aluminium slag. The leachates were also mitodepressive, and caused significant increases in the frequency of chromosome aberrations. These results demonstrate that the Allium test is a useful screening test for the evaluation and ranking of toxic industrial waste.
Cytotoxicity of MEIC Chemicals to Rainbow Trout R1 Cell Line and Multivariate Comparison with Ecotoxicity Tests
Authors: Segner Helmut , Schüürmann Gerrit
Published: August 2020

The cytotoxic effects of the first ten chemicals from the Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme on the fibroblast-like R1 cell line, derived from rainbow trout (Oncorhynchus mykiss), were measured by using three endpoints: cell attachment (24-hour exposure, crystal violet protein stain); cell viability (24-hour exposure, neutral red uptake cytotoxicity assay); and cell growth (144-hour exposure, crystal violet protein stain). The results were compared with published MEIC toxicity data from fish and mammalian cells, and from ecotoxicity tests with bacteria, invertebrates and plants by using multivariate statistical techniques. For eight of the ten compounds under consideration, a high degree of correlation in toxicity ranking between the various bioassays was observed, irrespective of the test systems or endpoints utilised. This similarity might be explained by the basal cytotoxicity concept. The 20% dissimilarity of the results, however, indicates the influence of test system-specific or end-point-specific sensitivities.
In Vitro Tests in Pharmacotoxicology: Can We Fill the Gap between Scientific Advances and Industrial Needs?
Authors: Shrivastava Ravi
Published: August 2020

The use of in vitro alternatives in pharmacotoxicological research has been a subject of continuous discussion among scientists, regulatory authorities and animal protection groups. Despite the fact that the validity and reliability of different in vitro models for replacing whole-animal experimentation have been scientifically proved, the routine use of in vitro tests remains limited. In the current industrial economic climate, I believe that, despite the simplicity and the predictive powers of the proposed in vitro models, the unfavourable cost:benefit ratio of some of these tests will remain an important barrier to the universal acceptance of in vitro alternatives.
An Animal Protection Sponsor's View of MEIC
Authors: Thurston Ethel
Published: August 2020

The Multicenter Evaluation of In Vitro Cytotoxicity programme is most important to animal protection, since it has validated 64 in vitro tests using advanced human data for 50 chemicals as the “gold standard”. Therefore, it has been able to compare animal cell tests, human cell tests and whole-animal tests fairly with unbiased scientific evidence. Added bonuses have included the identification and development of missing in vitro information (“missing tests”), publication of time-related lethal blood concentrations for all 50 chemicals, and some preliminary plans to resolve the 50,000 untested (or poorly tested) chemicals in the chemical mountain.
The activities of peptides “31–43”, “44–55” and “56–68” of A-gliadin on In Vitro Cultures of CaCo-2 Cells
Authors: Giovannini Claudio , Luchetti Roberto , De Vincenzi Massimo
Published: August 2020

In previous studies, various A-gliadin peptides with known amino acid sequences have been tested for their damaging effects on in vitro cultured atrophic coeliac mucosa. The largest common sequences among the in vitro toxic peptides were (gln) 3- pro and pro-ser-(gln)2. Three of these active A-gliadin fragments were synthesised and characterised, namely, the peptides corresponding to the amino acid sequences “31–43” and “44–55”, which contain the sequences (gln)3-rpro and pro-ser-(gln)2, respectively, and the “56–68” fragment lacking both active amino acid sequences. While the “56–68” A-gliadin peptide was completely inactive in CaCo-2 cells, the other two peptides were cytotoxic toward these cells to different extents. Our results confirm that CaCo-2 cells are a suitable model for the identification of toxic peptides responsible for coeliac pathogenesis.
In Vitro Versus In Vivo Propagation of Monoclonal Antibodies: A Test Case for the Effectiveness of Swedish Ethical Review Committees
Authors: Hansson Ulrika
Published: August 2020

In descriptions of the Swedish system for the control of animal experiments, it is often implied that the system guarantees that the animals are not subjected to unnecessary suffering and that available alternative methods are used. A study was carried out to examine applications for the use of the ascites method for monoclonal antibody production during 1995 and 1996. The data show that approval was given to all the applications received, with scanty justification. Thus, public reassurance that the Swedish system prevents the unnecessary use of animals is undermined by these findings.
Good Laboratory Practice and Study Management for the Validation of In Vitro Toxicity Studies
Authors: Cooper-Hannan Robin
Published: August 2020

The principles of Good Laboratory Practice (GLP) are designed to help ensure the proper management and conduct of studies. GLP compliance demonstrates to regulatory authorities that studies were undertaken in a manner which promotes confidence in the data and reporting. Formal validation of in vitro toxicity studies is being recommended as an inter-laboratory activity. Study management of interlaboratory studies in compliance with GLP is discussed. This includes: a) a clearly defined management, with responsibility for the GLP compliance of participating laboratories; b) one Study Director, who represents the single point of study control and who overviews study procedures and data, to ensure that procedures laid down in the protocol are being followed; and c) Principal Investigators, who may be appointed at some, or all, of the participating laboratories to facilitate supervision and communications with the Study Director.
The Effects of Two New Amphetamine-like Derivatives on the Phagocytic Ability of the Protozoan, Tetrahymena pyriformis
Authors: Alevisopoulos Giorgos , Stefanidou Maria , Pagou Margarita , Siatra-Papastaikoudi Theodora , Koutselinis Antonios
Published: August 2020

Six new amphetamine-like molecules (2-[2,3-dihydro-4 H-1,4-benzoxazine-4-yl]-1-methyl-2-[l-methyl-2-phenylethylamino] ethanamines) were synthesised and their physico-chemical behaviour was studied. The log P values (index of lipophilicity) of the derivatives were calculated according to Rekker's fragmental system. One derivative representative of each series (C-5508 and C-5512) was selected, and their biological effects on the phagocytic ability of the protozoan, Tetrahymena pyriformis, were studied as a basic functional test for an amphetamine-like action. Furthermore, the action of both derivatives when administered concomitantly with haloperidol was also investigated. The data indicate that both derivatives significantly increased the phagocytic ability of the protozoan (p < 0.001), presumably via an alternative pathway to that of one of the dopamine monoaminergic pools. The administration of haloperidol significantly suppressed phagocytosis (p < 0.001). However, cultures exposed to the derivatives and to haloperidol indicated quantitatively different reactions. The lipophilic behaviours of the derivatives provide & possible explanation for such distinct effects.
A Quantitative Structure-toxicokinetic Relationship Model for Highly Metabolised Chemicals
Authors: Poulin Patrick , Krishnan Kannan
Published: August 2020

The aim of the present study was to develop a quantitative structure-toxicokinetic relationship (QSTkR) model for highly metabolised chemicals (HMCs). The proposed QSTkR model is essentially a physiologically based toxicokinetic (PBTK) model, in which the blood:air and tissue:blood partition coefficients (PCs) are predicted from the molecular structure of chemicals, and the liver blood flow rate (Q1) is used to describe hepatic clearance. Molecular structure-based prediction of the blood:air and tissue:blood PCs was performed from the n-octanol:water and water:air PCs of chemicals obtained with the conventional fragment constant methods. The validity of incorporating Q1 instead of metabolic rate constants, as the hepatic clearance factor, in PBTK models for HMCs (extraction ratio > 0.7) was verified by comparing the simulations of venous blood concentration (Cv) profiles obtained with both the QSTkR and PBTK model approaches for 1,1-dichloroethylehe, trichloroethylene and furan in the rat. Following the validation of this alternative approach for describing hepatic clearance of HMCs, a QSTkR model for dichloromethane was constructed. This model used molecular structure information as the sole input, and provided simulations of Cv for human exposure to low concentrations of dichloromethane. The QSTkR model simulations were similar to those obtained with the previously validated, conventional human PBTK model with experimentally determined PCs and metabolic rate constants (Vmax, Km and Kf) for dichloromethane. The present methodology is the first validated example of a mechanistically based prediction of the inhalation toxicokinetics of HMCs made solely from information on molecular structure.
Alternative Methods for Skin Irritation Testing: The Current Status
Authors: Botham Philip A. , Earl Lesley K. , Fentem Julia H. , Roguet Roland , van de Sandt Johannes J.M.
Published: August 2020

The ECVAM Skin Irritation Task Force was established in November 1996, primarily to prepare a report on the current status of the development and validation of alternative tests for skin irritation and corrosion and, in particular, to identify any appropriate non-animal tests for predicting human skin irritation which were sufficiently well-developed to warrant ECVAM supporting their prevalidation/validation. The task force based its discussions around the proposed testing strategy for skin irritation/corrosion emanating from an OECD workshop held in January 1996. The following have been reviewed: a) structure-activity and structure-property relationships for skin corrosion and irritation; b) the use of pH and acid/alkaline reserve measurements in predicting skin corrosivity; c) in vitro tests for skin corrosion; d) in vitro tests for skin irritation (keratinocyte cultures, organ cultures, and reconstituted human skin models); and e) human patch tests for skin irritation. It was apparent that, although several promising candidate in vitro tests for skin irritation (for example, reconstituted human skin methods, and human and animal skin organ culture methods) were under development and evaluation, a test protocol, a preliminary prediction model and supporting data on different types of chemicals were only available for a method employing EpiDerm™. Thus, it is proposed that this EpiDerm test undergoes prevalidation during 1998. In addition, since it was felt preferable to be able to include other in vitro tests in such a prevalidation study, it is recommended that a “challenge” be set to anyone interested in taking part. This involves submitting data on ten test chemicals selected by the task force, obtained according to a standard protocol with a preliminary prediction model, for review by the task force by 31 May 1998.
A Comparison of the Acute and Chronic Effects of Antidepressants in Cultured C6 and 1321N1 Cells
Authors: Slamon N. Debbie , Pentreath Vic W.
Published: August 2020

The cytotoxicities of the antidepressants amitriptyline, imipramine (both tricyclic), fluoxetine (a selective serotonin re-uptake inhibitor) and tranylcypromine (a monoamine oxidase inhibitor) were compared in vitro in rat (C6) glioma and human (1321N1) astrocytoma cell lines. Differences in toxicity were determined after acute (24-hour) and chronic (7-day) administration and assessed by using the neutral red uptake (NRU) assay, the MTT assay, increased expression of glial fibrillary acidic protein (GFAp), and reactive morphology criteria. The relative toxicities (EC50 [concentration causing an effect in 50% of cells] value range) were fluoxetine > amitriptyline > imipramine > tranylcypromine for all the tests employed, in both cell lines and at both exposure times. There was a high and significant positive correlation between the different cell types, at both exposure times, with both the NRU and MTT assays. Increases in MTT reduction, NRU, and GFAp expression associated with cell activation were noted in C6 cells after exposure for 24 hours, but decreased after exposure for 7 days. For 1321N1 cells, increases in NRU were only observed after exposure for 24 hours. Reactive-type changes in morphology were seen after exposure to all the antidepressants, in both the C6 and 1321N1 cell lines. The data show that low concentrations of antidepressants induce metabolic changes in the astrocyte cell lines, with some significant differences in the patterns of toxicity of the tested substances.
MEIC Evaluation of Acute Systemic Toxicity
Authors: Clemedson Cecilia , Barile Frank A. , Ekwall Barbro , Gómez-Lechón Maria José , Hall Tony , Imai Koichi , Kahru Anne , Logemann Pam , Monaco Francesca , Ohno Tadao , Segner Helmut , Sjöström Michael , Valentino Matteo , Walum Erik , Wang Xianhai , Ekwall Björn
Published: August 2020

Results from tests on the first 30 MEIC reference chemicals in 16 different systems are presented as a prerequisite to the subsequent in vitro/in vivo comparisons of acute toxicity data, i.e. the final MEIC evaluation of all test results of the study. The study is a supplement to the previously published results from 68 methods (including methods 45B and 46B [old numbers]) used to test the same set of chemicals. The strategies and methods of the preceding paper were employed to enable a comparative cytotoxicity analysis of the results from these 68 methods and from the 16 new methods to be made. Principal components analysis (PCA) of 82 assays demonstrated a dominating first component which described as much as 83% of the variance in the toxicity data. This remarkable similarity of all toxicity data was the main finding of the present study, and confirmed the results of the previous study with a less-extensive database. Also, the influence on the general variability of results of several key methodological factors was evaluated by analysis of selected sets of data, including linear regression of the results of pairs of methods, which were similar in all respects except for the factor under analysis. This analysis of the same 82 assays as before also confirmed previous results from the 68 assay database: a) the toxicities of a third of the chemicals increased considerably with exposure time; b) in general, cytotoxicity for human cells was well predicted by cytotoxicity tests with animal cells; c) this prediction was poor for two chemicals, i.e. digoxin and malathion; d) prediction of human cytotoxicity by ecotoxicological tests was only fairly good; e) 25 comparisons of similar assays employing different cell lines showed strikingly similar toxicities (mean R2 = 0.86); f) 22 comparisons of similar pairs of assays employing different primary cultures and cell lines also revealed similar toxicities (mean R2 = 0.79); and g) 15 comparisons of similar assays with different growth/viability endpoint measurements demonstrated strikingly similar toxicities (mean R2 = 0.89). Results b, e, f and g must be the main causes of the general similarity of results, while results a, c and d, together with other factors, could explain the 20% dissimilarity. These findings support the basal cytotoxicity concept and may assist in guiding and refining in vitro toxicity testing in the future.
The most important attributes for talented students who want to be scientists
Authors: Szabó János , Révész Habil György , Van-Dyke David J
Published: August 2020

This study aims to assess the views of Hungarian professors/associate professors regarding important student factors at the beginning of their scientific and academic careers. Two hundred seventy-three university faculty members who work with high-achieving students (e.g., gifted, honors) completed a questionnaire regarding the attributes of gifted students. The study highlights similarities and differences among these Hungarian faculty opinions on student attributes. Data was analyzed for talent-attributes with a logistic regression to discern the differences among different scientific disciplines (medicine, humanities, economics). A one way ANOVA model was used and indicated no difference between traits based on scientific discipline (F = 1.023; df = 5; p > 0.05). The conclusions of this research highlight key attributes of Hungarian honor students identified by Hungarian university teachers and these attributes are closer than we hypothesized related across scientific disciplines.
Satisfaction with democracy in Turkey: Findings from a national survey
Authors: Akboga Sema , Sahin Osman
Published: August 2020

A variety of factors affect citizens’ satisfaction with democracy. Based on Turkey’s political and economic context, as well as the existing literature, this study investigates the effect of four factors on people’s satisfaction with democracy in Turkey: citizens’ conceptualizations of democracy, being a political winner, citizens’ perceptions of electoral integrity, and ethnic identity. Regression analysis of a nationally representative survey reveals that political losers and those with negative perceptions of electoral integrity are less satisfied with democracy in Turkey, while people’s conceptualizations of democracy and ethnic identity do not have an effect on satisfaction with democracy. We conclude that, in Turkey, political polarization and negative perceptions of electoral integrity trigger a decline in citizens’ satisfaction with democracy, which requires the attention of policymakers.
Alternative technique of long acting cardioplegia delivery results in less hemodilution
Authors: Ong Geok Seen , Guim Goh Si , Lim Qi Xuan , Chay-Nancy Huang Shoo , Jaafar Nurdiyana Binte , Lim Clara Anne , Clement Chew Kai Hong , Sazzad Faizus , Kofidis Theo
Published: August 2020

Background:

Preparation of del-Nido cardioplegia and its delivery technique can cause significant hemodilution. The resultant effects from hemodilution are largely proportionate to the use of a dual circuit. We opted for a custom-disposable single cardioplegia circuit instead of a dual circuit.

Methods:

We describe an alternative technique of del-Nido cardioplegia delivery and initial clinical experience with it at National University Hospital, Singapore. This is a retrospective analysis of data from January 2017 to April 2019, comprising of 177 patients of heart surgery and reflecting a single center database survey under the National Health Care Group.

Results:

Of the 177 patients who underwent surgery with del-Nido cardioplegia, 76 (42.9%) were valve-only procedures and 5 (2.8%) were coronary artery bypass graft–only procedures. Ultrafiltration was utilized in 132 (62.6%) patients, whereas filtrate volume was 2200 [150-9500] mL. The alternative technique of del-Nido cardioplegia delivery adopted by National University Hospital advocates for a single pump, single circuit system. The retrospective institutional data highlighted safe delivery of del-Nido cardioplegia using this technique in a range of procedures.

Conclusion:

Besides the safe delivery of del-Nido cardioplegia, the National University Hospital Technique reduces hemodilution and provides other technical benefits including a steeper temperature gradient, modification of circuit configuration to deliver another cardioplegia while on bypass, as well as re-configuration of clamps to spike the base solution.
Ultrasound assessment of normal liver, spleen, and kidney dimensions in southwest Nigerian children: a bedside formula for sonologists
Authors: Akinlade Folasade T , Asaleye Christianah M , Ayoola Oluwagbemiga O , Aremu Ademola A
Published: August 2020

Background

Knowledge of the normal sizes of the liver, spleen, and kidneys is important to radiologists when assessing for pathology using ultrasound scan. The need for a local determination of a easy-to-use formula for estimating the expected normal sonographic dimensions of these organs in children in order to serve as baseline when assessing them for pathology cannot be over emphasized.

Purpose

To determine ultrasonographic sizes of the liver, spleen, and kidneys among primary school children in southwestern Nigeria and correlate these with anthropometric measures to provide local reference data and an easy-to-use formula for assessing these organs for pathology in clinical practice.

Material and Methods

This is an observational, cross-sectional study using 1000 public primary school children in Ogbomoso. Sonographic dimensions of their liver, spleen, and both kidneys with anthropometric parameters were obtained and correlated. Data were analyzed using SPSS version 20.

Results

The liver span was higher in boys than in girls ( P = 0.048) while the left lobe of the liver was higher in girls than in boys ( P = 0.003). The spleen length was higher in boys than in girls ( P = 0.011). There was no gender difference in kidney dimensions ( P > 0.05). All anthropometric measures correlated significantly ( P < 0.001) with organ dimensions. Body surface area is the strongest predictor of the liver and kidney sizes ( P < 0.001) and height for spleen size ( P < 0.001).

Conclusion

Nomograms for the liver, spleen, and kidneys and regression equations for estimating the dimensions of these organs were formulated based on the best multivariate correlates.
Computed tomography and magnetic resonance imaging findings of nasal chondromesenchymal hamartoma in a young child: a case report
Authors: Cui Ya-qiong , Wang Li-li , Huang Gang , Zhao Lian-ping
Published: August 2020

Nasal chondromesenchymal hamartoma (NCMH) is a rare destructive benign neoplasm that predominantly develops in infants and young children. The lesion is usually located in the nasal cavity, often in the adjacent paranasal sinuses and orbital region and especially in the ethmoid sinus. Because the imaging characteristics of NCMH often mimic the features of malignant tumors, it is clinically important to study the radiographic appearance of this disease. Therefore, we herein present the computed tomography and magnetic resonance imaging findings of NCMH occurring in a 7-year-old girl. The mass was resected via an endoscopic surgical approach and definitively diagnosed as NCMH based on histologic and immunohistochemical analysis. However, signs of tumor recurrence manifested 45 months after surgery. NCMH can be locally aggressive with an expansive and destructive radiographic appearance, which highly implies a malignant neoplasm. Hence, an accurate diagnosis is essential to avoid potentially harmful therapies, and detailed computed tomography or magnetic resonance imaging should be performed prior to surgery. Selective arterial embolization is also an important part of preoperative management because the degree of enhancement may not be adequate to determine the blood supply of the tumor. Moreover, complete radical excision cannot guarantee that the lesion will not recur.
Infiltration of synovitis into the flexor tendon: a case report
Authors: Jin Qianjun , Zhou Haiying , Lu Hui
Published: August 2020

Synovitis is a type of aseptic inflammation that occurs within joints or surrounding tendons. No previous reports have described a hypertrophic synovium eroding the tendon sheath and manifesting as synovitis within the flexor tendon. We herein report a case involving a 10-year-old girl who presented to our hospital with a 1-month history of a swollen mass and progressive inability to completely flex her left index finger. The active flexion angle of the proximal interphalangeal joint was limited to 85°. A longitudinal incision of the flexor digitorum profundus tendon was surgically performed. The synovium inside and outside the flexor digitorum profundus tendon was completely removed. After the surgical excision, normal tendon gliding returned without recurrence by the 1-year follow-up. The active flexion angle of the proximal interphalangeal joint improved to 100°. To the best of our knowledge, this is the first case of synovitis affecting the flexor tendon and leading to limited flexion of a finger. The manifestation of a double ring sign on magnetic resonance imaging is quite characteristic. Early diagnosis and monitoring of the hyperproliferation and invasiveness of the synovial tissue are required. Surgical excision can be a simple and effective tool when necessary.
Effects of statins on clinical outcomes in hospitalized patients with community-acquired pneumonia
Authors: Zeenny Rony M. , Mansour Hanine , Kabbara Wissam K , Chamoun Nibal , Audi Myriam , Yared Yasmina , Salameh Pascale
Published: August 2020

Objective

We evaluated the effect of chronic use of statins based on C-reactive protein (CRP) levels and hospital length of stay (LOS) in patients admitted with community-acquired pneumonia (CAP).

Methods

We conducted a retrospective study over 12 months at a teaching hospital in Lebanon comparing patients with CAP taking chronic statins with patients not taking statins. Included patients with CAP were older than age 18 years and had two CRP level measures during hospitalization. CURB-65 criteria were used to assess the severity of pneumonia. A decrease in CRP levels on days 1 and 3, LOS, and normalization of fever were used to assess the response to antibiotics.

Results

Sixty-one patients were taking statins and 90 patients were not taking statins. Patients on statins had significantly more comorbid conditions; both groups had comparable CURB-65 scores. In both groups, no statistically significant difference was seen for the decrease in CRP level on days 1 and 3 and LOS. No difference in days to normalization of fever was detected in either group.

Conclusion

No association was found between the chronic use of statins and CRP levels, LOS, or days to fever normalization in patients with CAP.
Variegated transitions: Emerging forms of land and resource capitalism in Laos and Myanmar
Authors: Kenney-Lazar Miles , Mark SiuSue
Published: August 2020

Since the mid- to late- 1980s, Laos and Myanmar (Burma) have gradually and unevenly opened their economies to capitalist relations of accumulation. Both countries have done so by granting state land concessions to private capital for resource extraction and land commodification projects, particularly since the early 2000s. Yet, resource capitalism has manifested in distinct ways in both places due to the ways in which capital has interacted with unique pre-capitalist political-economic and social relations as well as the diverse political reactions of Lao and Myanmar people to capitalist transformations. In this paper, we analyze such differences through a conceptualization of ‘variegated transitions’, an extension of the variegated capitalism framework, which investigates the political economic transitions towards capitalism in marginalized, resource extractive countries of the Global South. In Myanmar, the transition from military to democratic rule has been marked by protests and land occupations combined with center-periphery fragmentation and ongoing civil wars, all of which have led to a heavily contested process of land concession granting. In contrast, a stable, comparatively centralized political system in Laos that restrains popular protest has enabled an expanding regime of land concessions for resource extraction projects, albeit hemmed in at the edges by sporadic, localized forms of resistance and appeals to the state.
Gene-modified BMSCs encapsulated with carboxymethyl cellulose facilitate osteogenesis in vitro and in vivo
Authors: Zheng Shicong , Chen Hanzheng , Zhang Tingshuai , Yao Yongchang , Chen Yi , Zhang Shujiang , Bai Bo
Published: August 2020

Critical size bone defects are one of the most serious complications in orthopedics due to the lack of effective osteogenesis treatment. We fabricated carboxymethyl cellulose with phenol moieties (CMC-ph) microcapsules loaded with gene-modified rat bone mesenchymal stem cells (rBMSCs) that secrete hBMP2 following doxycycline (DOX) induction. The results showed that the morphology of microcapsules was spherical, and their diameters have equally distributed in the range of 100–150 μm; the viability of rBMSCs was unchanged over time. Through real-time PCR and Western blot analyses, the rBMSCs in microcapsules were found to secrete hBMP2 and to have upregulated mRNA and protein expression of osteogenesis-related genes in vitro and in vivo. Furthermore, the in vivo results suggested that the group with the middle concentration of cells expressed the highest amount of osteogenic protein over time. In this study, we showed that gene-modified rBMSCs in CMC-ph microcapsules had good morphology and viability. The BMP2–BMSCs/CMC-Ph microcapsule system could upregulate osteogenic mRNA and protein in vitro and in vivo. Further analysis demonstrated that the medium concentration of cells had a suitable density for transplantation in nude mice. Therefore, BMP2–BMSCs/CMC-Ph microcapsule constructs have potential for bone regeneration in vivo.