bluuebunny/crossref_metadata_2025 huggingface dataset:
Salmonellosis Outbreak After a Large-Scale Food Event in Virginia, 2017
Authors: Shaw Kelly A. , Wright Kimberly , Privett Keith , Holloman Kelsey , Levine Seth , McCombs Katherine , Turner Lauren , Holsinger Caroline , Woolard Diane
Published: August 2020

Objectives

The Virginia Department of Health (VDH) identified an outbreak of Salmonella serotype Javiana infections in Virginia after a chili and chowder cook-off with 11 competitors and about 2500 attendees on September 30, 2017. The objectives of this study were to assess the extent of the outbreak and identify the most likely source of exposure.

Methods

To identify people with suspected Salmonella infection, VDH used press releases and social media posts to recruit event attendees to take an online survey about foods eaten at the cook-off and any gastrointestinal (GI) symptoms experienced. VDH defined a case as reported GI illness that occurred within 1 week after eating food from the cook-off. Confirmed cases required a clinical specimen culture positive for Salmonella. Probable cases reported diarrhea or related clinical symptoms. “Not ill” people did not report GI illness. Investigators calculated unadjusted relative risks of illness and performed stratified analysis to address potential confounding. Available food samples were tested for Salmonella. Environmental health specialists interviewed food handlers and inspected restaurants where 3 competitors had prepared food.

Results

Of 438 survey responses, 171 (39%) met the case definition. Of all chilies and chowders consumed, Chowder A was associated with the highest relative risk of illness (8.9; 95% CI, 5.7-13.7). A Chowder A sample tested positive for Salmonella serotype Javiana. The environmental investigation did not identify an original contamination source but did find deficiencies in maintaining safe cooking temperatures.

Conclusions

Epidemiologic and laboratory findings indicated that Chowder A was the most likely cause of outbreak. Recommendations to prevent future outbreaks include preparation of all food on-site to ensure safe temperatures during food preparation and service.
Characterization and empirical analysis of hot water immersion with compression protective performance of fabrics used in firefighters’ clothing
Authors: Mandal Sumit , Batcheller Jane , Song Guowen , Grover Indu Bala
Published: August 2020

This study aims to investigate hot water immersion with compression protective performance of textile fabrics used in firefighters’ clothing. This study has two key objectives – firstly, to characterize the protective performance of fabrics under different types of hot water immersion with compression exposures; secondly, to empirically analyze the protective performance of these fabrics under different exposures. To accomplish both the objectives, the physical properties (e.g., thickness, air permeability) of multi-layered fabrics that are commonly used in firefighters’ clothing were measured. Next, the protective performances of these fabrics were evaluated under different exposures. The experimental data obtained were statistically analyzed to identify the effects of the fabrics’ physical properties on the performance. Also, the performances provided by the fabrics were compared, and the nature of heat and mass transfer through the fabrics was explored. Using the significant fabric properties that affected the performance, Multiple Linear Regression (MLR) and Artificial Neural Network (ANN) modeling techniques were used to empirically predict the performance of the fabrics. The best prediction models were then employed for saliency testing to understand the relative importance of the significant fabric properties on the performance. The study demonstrates that the protective performance of textile fabrics varies with the exposures, depending upon the mass transfer through fabrics. In these exposures, fabric thickness, air or water-vapor permeability, and evaporative resistance are found to be the primary properties to consider in protecting the wearer. In this study, it has been identified that ANN models can be effectively used in comparison to MLR models for predicting the protective performance. By analyzing the best-fit ANN models, it is identified that different fabric properties play a key role in predicting the protective performance. Overall, this study would enhance the understanding of fabric materials used in firefighters’ clothing. This deeper understanding could be applied to engineer new test standards and fabric materials for clothing to provide optimum occupational health and safety for firefighters.
‘Post-pandemic’ transnational gentrifications: A critical outlook
Authors: Alexandri Georgia , Janoschka Michael
Published: August 2020

Transnational gentrifications have been occurring at the crossroads of capital investment fuelled to satisfy the remarkable increase of so-called leisure-oriented mobilities. Such mobilities, however, cause disruptive social, spatial and economic transformations of urban and rural landscapes across the globe. Consequently, transnational gentrifications may be considered a crucial testimonial of economic shifts, during the 2008–2020 period of accumulation. In this article, we argue that the underlying conceptual assumptions of transnational gentrifications require crucial adjustments. We should especially consider the intellectual roots that simply celebrate leisure-oriented mobilities while setting aside the exclusionary social practices of the consumption of space, culture, heritage and place. We do this by interpreting the phenomenon by means of a political economy that understands (i) the lens of the multi-scalar organisation of state power as a centrepiece for orchestrating the conditions for transnational gentrifications; (ii) transnational middle-class leisure-oriented mobilities linked dichotomously with labour precariousness and flexibility; and (iii) the rent gap as an analytical tool to understand dispossession, and corresponding displacement of people, practices and discourses. This approach sheds light on the nuances of gentrification as an attribute of systemic violence exercised in financialised capitalism. It also supports us to sketch out a theoretically informed outlook for the ongoing reorientation of intertwined gentrifications by transnational capital investments with intermittent flows of people in the aftermath of the COVID-19 pandemic.
From geopolitics to geotechnics: global futures in the shadow of automation, cunning machines, and human speciation
Authors: Grove Jairus
Published: August 2020

This exploration provides an alternative future to that offered in the discussions surrounding what is often referred to by the ‘fourth industrial revolution’ or the ‘third offset’. I argue that even modest projections of existing trends have the capability of altering the grammar or ecology of geopolitics as well as the drivers for competition and catastrophe. Such changes are more significant than questions of how this or that actor might be different or which great powers may shape the international order in a hundred years. The essay seeks to understand what disruptive changes in non-human capability might mean for the shape of a potential geopolitics to come. In a more general sense, I want to think about how violence will be distributed differently. Will there be new sources and even kinds of competition unique to a global system populated and in some cases, structured by cunning machines – some mechanical, others digital – and what are the implications for how we imagine international relations?
Tourism, Institutions, and Poverty Alleviation: Empirical Evidence from China
Authors: Zhao Lei
Published: August 2020

While tourism can be advocated as a means for poverty reduction, the inconclusive issue of poverty in developing countries has harbored doubts about the efficacy of tourism development in its reduction. This study empirically examines whether institutions influence how tourism development affects poverty. We apply the system generalized method of moments technique to estimate our empirical model. By using panel data for 29 Chinese provinces over the period 1999 to 2014, we empirically reveal that tourism and institutions have significant and negative effects not only on the absolute poverty but also on the relative poverty as measured by the Foster–Greer–Thorbecke (FGT) poverty indices in both the short and long run albeit at varying magnitudes of effect and levels of significance. In addition, institutional quality positively moderates the tourism–poverty nexus, thereby suggesting that the pro-poor effect of tourism development decreases as the quality of institutions improves in the thin institutional setting of rural China.
Assessment of Anxiety in Long-Term Care Residents: Issues and Strategies
Authors: Pifer Marissa A. , Segal Daniel L. , Jester Dylan J. , Molinari Victor
Published: August 2020

The experience of clinically significant anxiety and anxiety disorders represent significant and often debilitating problems for many residents in long-term care (LTC) settings. However, anxiety problems often go undetected and untreated in this growing population. The purposes of this paper are to examine the prevalence and impact of anxiety problems among residents in LTC facilities, describe the efficacy of the current instruments that are used to detect anxiety in these settings, and provide clinical guidance for the thorough assessment of anxiety. Regarding measurement tools, the GAI, GAI-SF, GAS-LTC, and the BADS are the only self-report measures designed for older adults that have been successfully validated for use with older adults living in LTC settings. Clinicians should focus on ways to educate LTC directors and staff to emphasize the importance of screening and assessing for anxiety, using validated measures, to improve the assessment and treatment of anxiety in their residents.
Synergistically improving the anti-reversion property of natural rubber by zinc glycerolate and zinc laurate as environmentally friendly activators
Authors: Yang Shunyu , Pan Qiwei , Chen Zhaohui
Published: August 2020

Sulfur-vulcanized nature rubber (NR) usually accompanies with reversion, which is of great challenge to the application of the NR products. In this work, zinc glycerolate in combination with zinc laurate was incorporated into sulfur-vulcanized NR, for the purpose of effectively substituting the traditional activator zinc oxide. Curing characteristics, physical and mechanical properties and dynamic viscoelastic behavior of the sulfur-vulcanized NR were investigated. Compared with solo addition of zinc glycerolate, zinc glycerolate/zinc laurate significantly improved the anti-reversion property of the sulfur-vulcanized NR. Incorporation of zinc laurate also enhanced the processing fluidity, filler dispersion, and rolling resistance of the sulfur-vulcanized NR. Moreover, the mole fraction of zinc was reduced by 51% with using zinc glycerolate/zinc laurate, compared with the traditional vulcanizates activated by zinc oxide. Our work provides a green approach to fabricate sulfur-vulcanized NR with outstanding anti-reversion performance.
Formation of Informal Settlements and the Development of the Idiom Teneke Mahalle in the Late-Ottoman Istanbul
Authors: Yılgür Egemen
Published: August 2020

A teneke mahalle, mostly consisting of shacks constructed of collected waste materials, is a late Ottoman and early Republican phenomenon that parallels its global counterparts such as the Corralones in Peru or the Indian slums. Although occasionally mentioned in the pioneer studies, the long history of the teneke mahalles has been overlooked until recent times, and in the mainstream discussions on urban poverty, these neighborhoods have almost wholly been invisible. However, informal settlements came to the agenda of the state and society, right after the massive eviction in 1883 of the refugees of the War of 1877-1878 from the free temporary settlements. They created teneke mahalles, and over time, the local poor also adopted their creative solution for cheap and relatively safe housing. Drawing on both archival and oral records, the author establishes the actual presence of the category and traces the development of the idiom in the late nineteenth century.
Accommodating Foreigners in a Littoral Borderland: The Lower Pearl River Delta during the Opium War
Authors: Luk Gary Chi-hung
Published: August 2020

This article traces the Chinese accommodation of foreigners in the lower section of the Pearl River delta during the Opium War to the region’s social ecology in late imperial times. With a long tradition of living with foreign sojourners and their vessels, Chinese people in the delta congregated on an unprecedented scale at the outer anchorages within the present-day Hong Kong region in 1839–1841 to trade with Euro-American merchants and the British expedition. As mobile and violent provisioners and opium dealers, they flourished in the littoral borderland between the Qing and British empires. Their cross-shore ventures constituted an intensification of their prewar activities and an economic adaptive strategy in the competitive society of mid-Qing Guangdong. Centering on the socioeconomic lives of ordinary Chinese people, this article problematizes the usage of “Hanjian” and “collaboration” as nationalist and statist labels to summarize Chinese assistance to foreigners in times of external war in modern China.
Artistic work intermediaries as industrial relations institutions: The case of musicians
Authors: Lizé Wenceslas , Greer Ian , Umney Charles
Published: August 2020

In artistic and cultural work, where unions and formal industrial relations institutions have weak influence, market intermediaries often shape the terms of exchange for workers. Focusing on musicians and drawing mainly on examples from France, this article shows how these intermediaries shape employment relations, in particular the distribution of risks and surpluses. While intermediaries and musicians have many shared interests, there is also a structural antagonism between them, which could be exacerbated by digitalization.
A ‘place-based’ approach to work and employment: The end of reciprocity for ordinary working families and ‘giggers’ in a place
Authors: Clark Ian , Lawton Chris , Stevenson Clifford , Vickers Tom , Dahill David
Published: August 2020

The authors define ‘place basing’ as the study of work and employment in a particular place. They are interested in understanding the limitations of work opportunities therein and so focus on workers and jobs that are not subject to the threat of off-shoring or relocation elsewhere but which are low paid and insecure. The authors theorize three contributions to new knowledge that flow from a place-based study of work and employment by demonstrating how precarious flexible often zero hour work eschews reciprocity between employer and employees and workers. They focus their research on ordinary working families and the ‘permissive visibility’ of bad work. The research points to an idealized model of individual and family economic functioning that is able to cope with physical and mental challenges individually without burdening the state. As the findings on workers and households demonstrate, this ideal is far from the reality they experience.
Neoplastic causes of nonacute facial paralysis: A review of 221 cases
Authors: Leonetti John P. , Marzo Sam J. , Anderson Douglas A. , Sappington Joshua M.
Published: August 2020

We conducted a retrospective review to assess the clinical presentation of patients with tumor-related nonacute complete peripheral facial weakness or an incomplete partial facial paresis and to provide an algorithm for the evaluation and management of these patients. Our study population was made up of 221 patients—131 females and 90 males, aged 14 to 79 years (mean: 49.7)—who had been referred to the Facial Nerve Disorders Clinic at our tertiary care academic medical center over a 23–year period with a documented neoplastic cause of facial paralysis. In addition to demographic data, we compiled information on clinical signs and symptoms, radiologic and pathologic findings, and surgical approaches. All patients exhibited gradual-onset facial weakness or facial twitching. Imaging identified an extratemporal tumor in 128 patients (58%), an infratemporal lesion in 55 patients (25%), and an intradural mass in 38 (17%). Almost all of the extratemporal tumors (99%) were malignant, while 91 % of the infratemporal and intradural tumors were benign. A transtemporal surgical approach was used in the 93 infratemporal and intradural tumor resections, while the 128 extratemporal lesions required a parotidectomy with partial temporal bone dissection. The vast majority of patients (97%) underwent facial reanimation. We conclude that gradual-onset facial paralysis or twitching may occur as a result of a neoplastic invasion of the facial nerve along its course from the cerebellopontine angle to the parotid gland. We caution readers to beware of a diagnosis of “atypical Bell's palsy.”
Parotid gland metastasis in Merkel cell carcinoma of the head and neck: A series of 14 cases
Authors: Day Kristine E. , Carroll William R. , Rosenthal Eben L.
Published: August 2020

Merkel cell carcinoma (MCC) is a rare cutaneous cancer of neuroendocrine cell origin that occurs frequently on the head and neck. With a high incidence of local recurrence and regional and distant metastasis, it carries a poor prognosis. We performed a retrospective study to determine the prognostic implications of parotid gland metastasis in MCC of the head and neck. Our study population was made up of 14 patients—13 men and 1 woman, aged 62 to 87 years (mean: 75.9)—who underwent a parotidectomy for the diagnosis of MCC over a period of 10 years and 9 months. Ten patients had a primary skin lesion of the head and neck and 4 presented with a parotid mass and an unknown primary. In all, 13 of the 14 patients were found to have parotid involvement—either a direct extension of MCC into the gland or a positive intraparotid lymph node; some patients had both. All patients underwent tumor excision, and 10 underwent neck dissection. Eleven patients received adjuvant radiotherapy; none received adjuvant chemotherapy. Of the 10 patients who underwent a neck dissection, 6 were found to have a cervical lymph node metastasis on pathologic examination. Follow-up ranged from 1.3 to 39.2 months (mean: 12.4). Three patients were lost to follow-up shortly after surgery, although some information was available on 2 of them. At the final follow-up, mortality data were available on 12 patients; of these, 11 had died. The lone survivor was the patient without a parotid metastasis. Among those known to have died, survival ranged from 1.6 to 49.2 months (mean: 16.0). We conclude that parotid metastasis in patients with MCC of the head and neck is associated with a dismal survival rate that is even worse than the poor survival associated with cervical node involvement.
The Lebensform as organism: Clarifying the limits of immanent critique
Authors: Bodde Emerson
Published: August 2020

In this article, I argue for the necessary organicism of immanent critique and the resulting limits and applicability of immanent critique as elaborated in Rahel Jaeggi’s account of Lebensformen. Through a historical review of the problem of natural purposiveness between Kant, Schelling and Hegel, I show that the notion of immanent critique that Hegel produced, and Jaeggi adopts, was an intrinsically organic notion. With this conceptual connection, I demonstrate that Jaeggi’s elaboration of Lebensformen is consistent with this organicism, but also explicate how this property limits critique where the criterion is the long-term stability of Lebensformen. Aligning the organicism of immanent critique with similar projects of social criticism citing the organic, namely eco-Marxism and cybernetics, I show that the cases of capitalism and bureaucracy are not practically vulnerable to immanent critique without supplement. I conclude by suggesting further research requires articulating a hybrid external-immanent form of criticism.
Competing With Charter Schools: Selection, Retention, and Achievement in Los Angeles Pilot Schools
Authors: Kearns Caitlin , Lauen Douglas Lee , Fuller Bruce
Published: August 2020

Charter schools place competitive pressure on school districts to retain students and public funding. Many districts also have moved to decentralize control of budgets and teacher hiring down to school principals, independent of competitive pressures. But almost no evaluation evidence gauges the effectiveness of charter-like schools, relative to traditional public schools. We find that autonomous pilot schools in Los Angeles enroll more low-income and Spanish-speaking students, compared with traditional schools. Pilot pupils are significantly less likely to exit the school district. But pilot pupils displayed lower test scores in mathematics and fell slightly below traditional students in English-language arts, taking into account prior performance and their propensity to enter pilot schools. We tracked 6,732 students entering pilot high schools between 2008 and 2012, statistically matched in multiple ways with traditional peers from identical sending middle schools. We discuss the advantages of our evaluation strategy and the implications of our findings for education leaders and policy makers.
Aerosol-generating procedures in thoracic surgery in the COVID-19 era in Malaysia
Authors: Sathiamurthy Narasimman , Balasubbiah Narendran , Dharmaraj Benedict
Published: August 2020

Background

The Covid-19 pandemic has caused changes in the surgical treatment of non-Covid patients, especially in thoracic surgery because most procedures are aerosol generating. Hospital Kuala Lumpur, where thoracic procedures are performed, was badly affected. We describe our experience in performing aerosol generating procedures safely in thoracic surgery during the Covid-19 era.

Methods

Medical records of patients who underwent thoracic surgery from March 18, 2020 to May 17, 2020 were reviewed retrospectively. All patients undergoing thoracic surgery were tested for Covid-19 using the reverse transcriptase polymerase chain reaction method. Patients with malignancy were observed for 10 to 14 days in the ward after testing negative. The healthcare workers donned personal protective equipment for all the cases, and the number of healthcare workers in the operating room was limited to the minimum required.

Results

A total of 44 procedures were performed in 26 thoracic surgeries. All of these procedures were classified as aerosol generating, and the mean duration of the surgery was 130 ± 43 minutes. None of the healthcare workers involved in the surgery were exposed or infected by Covid-19.

Conclusion

Covid-19 will be a threat for a long time and thoracic surgeons must continue to provide their services, despite having to deal with aerosol generating procedures, in the new normal. Covid-19 testing of all surgical candidates, using the reverse transcriptase polymerase chain reaction, donning full personal protective equipment for healthcare workers, and carefully planned procedures are among the measures suggested to prevent unnecessary Covid-19 exposure in thoracic surgery.
In Vitro Screening for Hepatotoxicity of Xenobiotics using Isolated Hepatocytes
Authors: Lavrijsen Karel , Van Dijck Derk , Van Houdt Jos , Van Pelt Ingrid , Meuldermans Willem , Heykants Jos
Published: August 2020

Isolated hepatocytes from male rats were cultured in primary cell culture in 24-well dishes for 20–24 hours in the presence of the various test compounds. Cytotoxicity at the end of the culture period was evaluated by the determination of LDH-release into the culture medium or by quantification of DNA content as a measure of the cell number in each well. Toxic xenobiotics, such as chlorpromazine, were able to induce LDH-release at up to 5 times the background levels at concentrations of 10-4–10-5 M. For most compounds, the increase in LDH-release was closely related to a decrease in cell number, as measured by the DNA method. Two culture conditions which might influence the cytotoxic response were investigated. Prolongation of the culture time increased the toxicity of some compounds, e.g. sodium dodecylsulphate, whereas for other compounds, e.g. amitriptyline, no change was noted. Addition of serum albumin and α1-acid glycoprotein decreased the toxicity of chlorpromazine to isolated hepatocytes. These results indicate that isolated hepatocytes might represent a useful in vitro toxicity screening system, and that careful standardisation of the culture conditions is necessary.
Does Morphine Affect Astrocytes?
Authors: Rönnbäck Lars , Hansson Elisabeth
Published: August 2020

Astrocytes in primary culture express receptors for monoamine and peptide neurotransmitters. The cells also exhibit uptake sites for amino acid neurotransmitters. New data is presented, demonstrating interactions between the second messenger systems for vasoactive intestinal peptide (VIP) and α- and β-adrenoceptors. Stimulation of these monoamine receptors modulates GABA and glutamate uptake into the cells, which indicates that astrocytes have the capacity to supervise and regulate synaptic transmission. Morphine affects astrocytes directly, probably by interaction with α2 receptors, and indirectly by drug-induced ionic changes in the synaptic region, followed by changes in neurotransmission and protein synthesis.

Modulation of astroglial specific functions or metabolism might be one way to affect functional neuronal disturbances, including an approach toward understanding the underlying cellular mechanisms, e.g. tolerance.
2,4-Dichlorophenol and MCPA in a V79 Test
Authors: Fiskesjö Geirid
Published: August 2020

Two industrial chemicals, 2,4-dichlorophenol and 4-chloro-2-methylphenoxyacetic acid (MCPA), which have no toxic effects on the Chinese hamster cell line V79 alone, were tested for toxicity and mutagenicity in a cell-mediated test, where mixed-function oxidase (MFO) enzymes are active in the metabolism of xenobiotics.

For 2,4-dichlorophenol, a dose-dependent toxicity as well as a slight mutagenicity could be shown when oxygenation enzymes were present. A similar degree of toxicity in a plant test system (the Allium test) indicates a similar risk of damage from exposure to dichlorophenol treatments in both these systems.

MCPA did not induce any toxic or mutagenic effects at the concentrations tested. These results were not in agreement with previous results in plant material, where MCPA was clearly toxic at relatively low doses. However, since chlorophenols have been found in plants sprayed with phenoxyacetic acids, further investigations should be performed concerning potential risk to human beings.
Animal Experiments and their Alternatives in Psychiatry
Authors: Stevens Anthony
Published: August 2020

During the last twenty years, the most enthusiastic advocates of the use of animal models in the study of human psychiatric dysfunction have been Harlow and Suomi. In an influential paper, Induced Depression in Monkeys (1974), they argued that more extensive use of non-human primates

“would have great potential utility since many manipulations and measurements presently prohibited in human study by ethical and practical considerations could be readily performed on non-human primate subjects in well-controlled experimental environments.”

Harlow & Suomi concluded this paper with the following statement:

“The results obtained to date on induced depression in monkeys show that proper and profound depressions can be produced relatively easily by a variety of techniques. These induced depressions either bear a close resemblance to human depression or have such similarity as to suggest that closely correlated human and animal depressive patterns may be achieved with refined techniques. The results to date also provide adequate data for the conduct of meaningful researches on the effects of pharmacological agents which either enhance, inhibit or preclude the experimental production of depression. Further, the existence of firm and fast monkey depression syndromes offers vast opportunities for testing a wide range of therapeutic techniques, either behavioural or biochemical.”
The Hep G2 Cell Line as a Possible Alternative to Isolated Hepatocytes in Cytotoxicity Studies
Authors: Marinovich Marina , Lorenzo Jose L. , Flaminio Liliana M. , Granata Agnese , Galli Corrado L.
Published: August 2020

The hepatotoxicity of carbon tetrachloride (CC14) was evaluated in vitro in freshly isolated rat hepatocytes and in the human hepatoma cell line, Hep G2. Toxicity was assessed by the leakage of cytosolic enzymes (lactate dehydrogenase and aspartate aminotransferase) and cell viability (trypan blue exclusion). The established human cells were less sensitive to CCl4-induced injury; higher doses of the toxic agent and longer incubation times were necessary to elicit cell damage.

Micromolar concentrations of prostaglandin E2 significantly decreased enzyme leakage in both Hep G2 cells and rat hepatocytes challenged with CC14; a stable derivative of prostacyclin (ZK 36374) was ineffective. These results suggest that human hepatoma Hep G2 cells may represent a valid alternative to isolated rat hepatocytes for an initial approach to the in vitro evaluation of cell toxicity.
Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics
Authors: Ferro Margherita , Bassi Anna Maria , Nanni Giorgio
Published: August 2020

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes.

The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids.

As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase.

The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.
Interaction of Neutrophils with Endothelial Cells, Fibroblasts and Their Extracellular Matrices: Microscopic and Computerised Analysis
Authors: Ziche Marina , Morbidelli Lucia , Rubino Annalisa , Dolara Piero , Bianchi Stefano , Fantozzi Roberto
Published: August 2020

Polymorphonuclear neutrophil (PMN) interaction with vascular endothelial cells is the initial event in the migration of neutrophils through blood vessel walls before reaching inflammation sites in tissues. The interaction between fibroblasts and endothelial cells and their extracellular matrices might be modulated by the activation of neutrophils that occurs at inflammatory reaction sites. We have used an in vitro model to study PMN function, measuring the adhesion of human PMNs to capillary endothelial cells and fibroblasts grown in culture and to their extracellular matrices. The interaction was measured in basal conditions and in the presence of the chemotactic effector, formyl-methionyl-leucyl-phenylalanine (FMLP at the concentration of 10 7M). Adhesion was expressed by the number of adherent PMNs/mm2 on a histological specimen. Moreover, we have adapted a program for image analysis to quantify neutrophil adhesion. Three times more PMNs adhered to matrices than to monolayers, and adherence could be increased by the presence of 10-7M FMLP, except in the case of fibroblast monolayers. We found a good correlation between microscopic observation and computerised image analysis measuring PMN adhesiveness to extracellular matrices.
An In Vitro Method for Examining the Effects of Human Monocytes on the Durability of Glass Fibres
Authors: Conroy Paul J. , Young John , Dewhurst David G. , Allen David W. , Clark Anthony
Published: August 2020

An in vitro method for characterising the degradation of glass fibres in an intramacrophage-type environment is reported. Human blood monocytes provide the phagocytically active cultures and a “semi-dynamic cell replenishment method”, whereby cultures are replenished every three weeks with monocytes from the same donor, has enabled exposure times exceeding 26 weeks to be achieved. Tests indicated an affinity of monocytes for glass fibre, and superoxide activity in freshly isolated cells was measured and found to be comparable with that for alveolar macrophages.
Computer Simulations in Teaching Neuromuscular Pharmacology—Time for a Change from Traditional Methods?
Authors: Brown Guy J. , Collins Godfrey G.S. , Dewhurst David G. , Hughes Ian E.
Published: August 2020

Two interactive computer programs are described which illustrate different approaches to teaching the pharmacology of neuromuscular transmission. Both programs are based on a simulation of the in vivo sciatic nerve–tibialis anterior muscle preparation of the cat. Program 1 simulates the preparation and allows students to follow a schedule set by the teacher, or design experiments themselves using drugs (including unknowns) and procedures selected from an extensive menu. The sequence of events and the doses used are entirely in the hands of the user and students “learn by discovery”. Program 2 is an interactive, computer-assisted learning package based on a software simulation of experiments which can be performed on this preparation to illustrate the fundamental pharmacology. The program is menu-driven, contains extensive textual information, makes use of animated graphics, and is accompanied by educational support material and assessments. Details of each program are presented and their use as alternatives to animal experiments is discussed in relation to the primary teaching objectives of practical classes.
Lead Interference in Actin Redistribution Induced by Chemotactic Peptide in Human Neutrophils
Authors: Governa Mario , Visonà Isabella , Valentino Matteo , Marchiseppe Isabella
Published: August 2020

The distribution of actin-containing structures in vitro was determined by fluorescence microscopy in human neutrophils exposed to two final concentrations of lead, 14.4μM and 28.8μM, stimulated with 10-8M formyl methyonylleucylphenylalanine (F-MLP) for either 45 seconds or 10 minutes, and then stained with phalloidin labelled with rhodamine. The comparison between untreated and lead-treated cells revealed that actin redistribution does not regularly occur within neutrophils in lead-containing medium. Immediately after F-MLP stimulation, no focal subcortical localisation of actin was observed. 10 minutes after stimulation, the redistribution of actin was considerably lower in the lead-treated cells than the redistribution which occurred within untreated cells. Moreover, the polarisation of neutrophils supplemented with lead was abortive.

Since previous investigations indicated that lead inhibits chemotaxis of neutrophils, these results suggest that one possible cause of this inhibition is related to an effect of lead on actin reorganisation within the cells.
Use of the Rainbow Trout Hepatoma Cell Line, RTH-149, in a Cytotoxicity Assay
Authors: Babich Harvey , Martin-Alguacil Nieves , Borenfreund Ellen
Published: August 2020

The rainbow trout hepatoma cell line, RTH-149, was evaluated for use as a bioindicator cell type in the neutral red cytotoxicity assay. The cells were exposed for six days to various polycyclic aromatic hydrocarbons, including chemicals that are direct-acting toxicants and chemicals that require enzymatic biotransformation to cytotoxic metabolites. Whereas benzo[a]pyrene was only slightly cytotoxic, its metabolites — (±)trans-7,8-diol-benzo[a]pyrene and 3-hydroxy-benzo[a]pyrene — were highly cytotoxic. 7,12-Dimethylbenz[a]anthracene was cytotoxic, but cytotoxicity did not occur with benzo[a]anthracene, benzo[b]fluoranthene and benzo[k]fluoranthene. This cell line appears to lack sufficient xenobiotic metabolising capacity to biotransform many of these polycyclic aromatic hydrocarbons to activated cytotoxic metabolites.
Cytotoxicity Evaluation of the First Ten MEIC Chemicals: Acute Lethal Toxicity in Man Predicted by Cytotoxicity in Five Cellular Assays and by Oral LD50 Tests in Rodents
Authors: Ekwall Björn , Bondesson Inger , Castell José V. , Gómez-Lechón Maria José , Hellberg Sven , Högberg Johan , Jover Ramiro , Ponsoda Xavier , Romert Lennart , Stenberg Kjell , Walum Erik
Published: August 2020

The MEIC (multicentre evaluation of in vitro cytotoxicity) programme is a five-year programme to validate in vitro tests for general toxicity, and is organised by the Scandinavian Society for Cell Toxicology. Interested laboratories are invited, on an international basis, to test 50 published reference chemicals in their respective assays. Submitted results will then be evaluated yearly by the MEIC Committee for their relevance to various types of human toxicity, including an evaluation for the same chemicals of the prediction by animal tests of human toxicity. To establish the validation methods, a preliminary validation cycle is being performed in 1989/90 with submitted results for the first ten MEIC chemicals. The present paper is the very first step of this preliminary validation process. The prediction of human toxicity by five cytotoxicity assays (altogether 14 different cell systems/endpoints) has been evaluated, and also compared with the predictive value of rodent LD50 tests. Mouse LD50 prediction of human lethal dosage for these substances was good, while rat LD50 prediction was less satisfactory. The collective predictions by all 14 cell systems/endpoints of human toxicity in the form of a multivariate PLS (partial least squares) model of human acute lethal blood concentrations, as well as the corresponding prediction by a HeLa cell assay, were comparable to the efficiency of mouse LD50 prediction of human lethal dosage. When combined with simple toxicokinetic data (absorption of chemicals in the intestine and distribution volumes), the PLS model and the HeLa assay were able to predict human lethal dosage of the ten chemicals as accurately as the mouse LD50 value. The small number of chemicals studied to date means that general conclusions cannot be drawn from these results. Further validation of more chemicals with the in vitro methods is essential and promises to be worthwhile.
Scoring of Cytotoxicity by Image Analysis using Animal Cell Cultures
Authors: Tillmann Utz , Pollet Dieter , Miltenburger Herbert G.
Published: August 2020

The estimation and assessment of toxic effects can be made clearer by direct observation of the target object — the living cell. Following this approach we continuously assess the reactions of cell cultures (at a range of densities) by using image analysis equipment. The parameters evaluated are: growth rate, alteration of cell cycle time, cell progeny, and mortality rate. The use of multi-well culture plates during the observation period enables the effects of different agents at different concentrations to be examined simultaneously under the same experimental conditions. The automatic observation of the fate of many individual cells permits the accurate quantification and characterisation of cytotoxic effects for the exposed cells and their progeny. Using this method, we have examined ethyl methanesulfonate (EMS), cetyltrimethyl-ammonium chloride (CTAC), and Na-aciclovir (NaA), and we demonstrate the distinction between reversible and irreversible cell damage.
Isolation and Maintenance of Continuous Cultures of Epithelial Cells from Chemically-injured Adult Rabbit Lung
Authors: Houser Sandra , Borges Lolita , Guzowski Dorothy E. , Barile Frank A.
Published: August 2020

Acute alveolar injury commonly occurs as a result of exposure to a variety of toxic stimuli and is characterised by widespread necrosis of the epithelium, followed by regeneration and hyperplasia of type II alveolar epithelial cells. We studied epithelial proliferation in rabbit lung resulting from a chemical stimulus by isolating the mitotically active cells and establishing them in continuous culture.

Acute alveolar injury was induced in rabbits with two daily injections of N-nitroso- N-methylurethane (NNNMU). Four to six days after treatment, the lungs were enzymatically digested and a homogeneous monolayer of epithelial cells was established in culture. The cells displayed a typical cobblestone-like arrangement and cuboidal shape, and represented 95% of the cells isolated. The cultures exhibited contact inhibition and achieved a population doubling level of 11 ± 2. Their epithelial origin was confirmed by positive reactions for immunofluorescent cytokeratin, alkaline phosphatase, and the Papanicolaou stain. Ultrastructurally, the cells showed abundant rough endoplasmic reticulum with dilated cisternae, desmosomes, cytokeratin filaments, and lamellar-like structures early in culture. In addition, the cells accumulated paraquat in a manner similar to that shown by established epithelial cell lines. The results demonstrate that regenerating epithelial cells can be isolated and propagated in culture as a relatively homogeneous population. This system, which is designed to further understanding of the metabolic role of epithelial cells following acute injury, may serve as an in vitro model for pulmonary toxicity studies using a minimal number of animals.
The EYTEX™ System and the Neutral Red Uptake Inhibition Assay in Cultured Hep G2 Cells as Alternative Methods for In Vivo Eye Irritation Following the EEC Protocol
Authors: Dierickx Paul J. , Gordon Virginia C.
Published: August 2020

The neutral red uptake inhibition assay and the EYTEX™ system were investigated as alternative methods for the assessment of eye irritation, determined according to the EEC protocol. The 17 test chemicals used were mainly organic solvents. The xenobiotics were applied to Hep G2 cells for 24 hours at different concentrations. Neutral red uptake inhibition was then measured. The results are expressed as the NI50 value, which is the concentration of test compound required to induce a 50% reduction in neutral red uptake. The same chemicals were also tested as coded samples by the EYTEX™ test according to the manufacturer's directions. A nearly identical quantitative correlation was found for both in vitro methods with corneal opacity scores: r = 0.84 for EYTEX™ scores and r = 0.83 for log NI50, expressed in μg/ml. Whilst these correlations are certainly not perfect, it is clear that both in vitro methods can be used as valuable prescreening methods.
An RSPCA/FRAME Survey of the Use of Non-human Primates as Laboratory Animals in Great Britain, 1984–1988
Authors: Hampson Judith , Southee Jacqueline , Howell David , Balls Michael
Published: August 2020

A literature-based survey of the use of non-human primates as laboratory animals in Great Britain in 1984–1988 was carried out as a background to extending debate about the ethical and practical issues involved. The 289 publications considered were grouped in 15 subject areas and reviewed in terms of scientific purpose, methods employed, numbers and species of animals used, and their source, care and ultimate fate. In addition, the Association of the British Pharmaceutical Industry provided a comment on the use of non-human primates by pharmaceutical companies. Specific causes for concern were identified, and future prospects considered.
The Use of Animals in Behavioural Science Education in the USA: Finding Alternatives that Address Personal Concerns and Ethical Dilemmas
Authors: Cohen Perrin S. , Block Martin L.
Published: August 2020

In this paper, we describe our efforts to develop a humanitarian approach to the teaching of behavioural science using animals. Reduction, replacement and refinement of animal use in education are most useful if they help reconnect students and teachers with their underlying feelings, attitudes and ethical values related to animal usage. In order to initiate this reconnection process, we established the Northeastern University Center for Science Education (NUCASE) to encourage the dissemination of information and the development of projects that address ethical issues in college science curricula. Two directions that NUCASE has piloted using a humanitarian approach are outlined: an alternative to the traditional animal laboratory course in learning that uses student-run field experiments with feral pigeons in a park; and a conference designed to promote open interchange about personal concerns and ethical dilemmas in the use of animals in education.
Analogy Models for Prediction of Human Toxicity
Authors: Hellberg Sven , Eriksson Lennart , Jonsson Jörgen , Lindgren Fredrik , Sjöström Michael , Wold Svante , Ekwall Björn , Gómez-Lechón Maria José , Clothier Richard , Accomando Nancy J. , Grimes Angie , Barile Frank A. , Nordin Marika , Tyson Charles A. , Dierickx Paul , Shrivastava R.S. , Tingsleff-Skaanild Mette , Garza-Ocañas Lourdes , Fiskesjö Geirid
Published: August 2020

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.
In Vitro Alternatives for Ocular Safety Testing: An Outline of Assays and Possible Future Developments
Authors: Wilcox David K. , Bruner Leon H.
Published: August 2020

An increasing number of in vitro tests are being proposed as alternatives for animals in ocular safety testing. These in vitro systems use a variety of approaches and measure a broad range of endpoints, including cellular cytotoxicity and metabolism. We will briefly review the development and validation of these model systems. Several tests appear promising, and may prove useful as adjuncts in our current ocular safety assessment schemes. We will also discuss how these tests can most rapidly be brought to use in ocular safety assessment, and where efforts should be directed to develop more-highly predictive in vitro model systems for the future.