bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid bacterial foraging-particle swarm optimization technique for solving optimal reactive power dispatch problem
Authors: Reddy P. Lokender , Guduri Yesuratnam
Published: August 2020

This paper presents a hybrid evolutionary computation algorithm termed as hybrid bacterial foraging-particle swarm optimization (HBFPSO) algorithm, to optimal reactive power dispatch (ORPD) problem. HBFPSO algorithm merges velocity and position updating strategy of particle swarm optimization (PSO) algorithm and reproduction and elimination dispersal of bacterial foraging algorithm (BFA). The ORPD is solved for minimization of two objective functions; system real power loss and voltage stability L-index. The objective is minimized by optimally choosing the control variables; generator excitations, tap positions of on-load tap changing transformers and switched var compensators while satisfying their constraints and also the constraints of dependent variabl

es; voltages of all load buses and reactive power generation of all generators. The proposed approach has been evaluated on a standard IEEE 30 bus test system and 24 bus EHV southern region equivalent Indian power system. The results offered by the proposed algorithm are compared with those offered by other evolutionary computation algorithms reported in the recent state of the art literature and the superiority of the proposed algorithm is demonstrated.
Abstract P186: Position Effects Blood Pressure Measurement During Pregnancy
Authors: Brandt Debra S , Prunty April B , Zagoren Daniel M , Holm Madeline E , Brennan Molly S , Werner-Anderson Maria , Weiss Jesse M , Wiltgen Michaela R , James Shannon M , Gilbertson-White Stephanie H , Myers Monica C , Sanborn Amy N , Scroggins Sabrina M , Spring Joseph C , Davis Heather A , Santillan Mark K , Santillan Donna A
Published: August 2020

Hypertension in pregnancy is a leading cause of maternal morbidity and mortality. Studies demonstrate that body positions affect the blood pressure (BP) measurements and have led to guidelines for proper positioning by the ACC and AHA. However, studies excluded pregnant women and did not include all common patient positions, such as semi-Fowlers. These studies cannot be applied to pregnant women due to dynamic cardiovascular changes in pregnancy. We measured BP in pregnant women in inpatient and outpatient settings in various positions. These BPs were compared to the published ACC/AHA guideline position: seated with arms and feet supported. Trained team members used an aneroid sphygmomanometer and stethoscope and/or a validated electronic BP machine. There is no significant difference between BP measurements using a sphygmomanometer/stethoscope vs. an electronic BP machine in the ACC/AHA guideline position (systolic p=0.60 diastolic p=0.91). There was not a significant difference in either systolic or diastolic means in the semi-Fowlers position (at 45 degrees measured by goniometer) (systolic=0.60 diastolic=0.95). Positioning did affect the diastolic BP measurement in the seated without support position (p=0.01) and both the systolic (p< 0.001) and diastolic (p<0.001) measurements in the left lateral recumbent position. Our data demonstrate that an accurate BP measurement in pregnancy is dependent upon patient position. Monitoring BP position in left lateral recumbent may mask an elevated BP. This study also suggests that it may be possible to substitute semi-Fowlers position for reliable BP measurements when chair sitting is not practical, such as labor.
Interstage Home Monitoring for Infants With Single Ventricle Heart Disease: Education and Management
Authors: Rudd Nancy A. , Ghanayem Nancy S. , Hill Garick D. , Lambert Linda M. , Mussatto Kathleen A. , Nieves Jo Ann , Robinson Sarah , Shirali Girish , Steltzer Michelle M. , Uzark Karen , Pike Nancy A. ,   the American Heart Association Council on Cardiovascular and Stroke Nursing; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; and Council on Lifestyle and Cardiometabolic Health
Published: August 2020

This scientific statement summarizes the current state of knowledge related to interstage home monitoring for infants with shunt‐dependent single ventricle heart disease. Historically, the interstage period has been defined as the time of discharge from the initial palliative procedure to the time of second stage palliation. High mortality rates during the interstage period led to the implementation of in‐home surveillance strategies to detect physiologic changes that may precede hemodynamic decompensation in interstage infants with single ventricle heart disease. Adoption of interstage home monitoring practices has been associated with significantly improved morbidity and mortality. This statement will review in‐hospital readiness for discharge, caregiver support and education, healthcare teams and resources, surveillance strategies and practices, national quality improvement efforts, interstage outcomes, and future areas for research. The statement is directed toward pediatric cardiologists, primary care providers, subspecialists, advanced practice providers, nurses, and those caring for infants undergoing staged surgical palliation for single ventricle heart disease.
Effects of Epeleuton, a Novel Synthetic Second‐Generation n‐3 Fatty Acid, on Non‐Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers
Authors: Climax John , Newsome Philip N. , Hamza Moayed , Weissbach Markus , Coughlan David , Sattar Naveed , McGuire Darren K. , Bhatt Deepak L.
Published: August 2020

Background

Epeleuton is 15‐hydroxy eicosapentaenoic acid ethyl ester, a second‐generation synthetic n‐3 fatty acid derivative of eicosapentaenoic acid. The primary objective was to assess the effect of epeleuton on markers of nonalcoholic fatty liver disease (NAFLD) with post hoc analyses of cardiometabolic markers.

Methods and Results

In a multicenter, randomized, double‐blind, placebo‐controlled trial, 96 adults with nonalcoholic fatty liver disease and body mass index 25 to 40 were randomized in a 1:1:1 ratio to receive epeleuton 2 g/day, epeleuton 1 g/day, or placebo for 16 weeks. A total of 27% of patients had diabetes mellitus. Primary end points of changes in alanine aminotransferase and liver stiffness did not improve at week 16. Secondary and post hoc analyses investigated changes in cardiometabolic markers. Epeleuton 2 g/day significantly decreased triglycerides, very‐low‐density lipoprotein cholesterol, and total cholesterol without increasing low‐density lipoprotein cholesterol. Despite a low mean baseline hemoglobin A1C (HbA
1C
; 6.3±1.3%), epeleuton 2 g/day significantly decreased HbA
1c
(−0.4%;
P
=0.026). Among patients with baseline HbA
1c
>6.5%, epeleuton 2 g/day decreased HbA
1c
by 1.1% (
P
=0.047; n=26). Consistent dose‐dependent reductions were observed for fasting plasma glucose, insulin, and insulin resistance indices. Epeleuton 2 g/day decreased circulating markers of cardiovascular risk and endothelial dysfunction. Epeleuton was well tolerated, with a safety profile not different from placebo.

Conclusions

While epeleuton did not meet its primary end points on alanine aminotransferase or liver stiffness, it significantly decreased triglycerides, HbA
1C
, plasma glucose, and inflammatory markers. These data suggest epeleuton may have potential for cardiovascular risk reduction and nonalcoholic fatty liver disease by simultaneously targeting hypertriglyceridemia, hyperglycemia, and systemic inflammation. Further trials are planned.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT02941549.
Education Level and Long‐term Mortality, Recurrent Stroke, and Cardiovascular Events in Patients With Ischemic Stroke
Authors: Che Bizhong , Shen Suwen , Zhu Zhengbao , Wang Aili , Xu Tan , Peng Yanbo , Li Qunwei , Ju Zhong , Geng Deqin , Chen Jing , He Jiang , Zhang Yonghong , Zhong Chongke
Published: August 2020

Background

Epidemiological studies have reported discrepant findings on the relationship between education level and outcomes after stroke. We aimed to prospectively investigate the relationship between education level and mortality, recurrent stroke, and cardiovascular events in Chinese patients with ischemic stroke.

Methods and Results

We included 3861 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Education level was categorized as illiteracy, primary school, middle school, and college. Study outcomes were all‐cause mortality, stroke‐specific mortality, recurrent stroke, and cardiovascular events within 2 years after ischemic stroke. A meta‐analysis was conducted to incorporate the results of the current study and previous other studies on the association of education level with outcomes after stroke. Within 2 years after ischemic stroke, there were 327 (8.5%) all‐cause deaths, 264 (6.8%) stroke‐specific deaths, 303 (7.9%) recurrent strokes, and 364 (9.4%) cardiovascular events, respectively. The Kaplan–Meier curves showed that patients with the lowest education level had the highest cumulative incidence rates of all‐cause mortality, stroke‐specific mortality, and cardiovascular events (log‐rank
P
≤0.01). After adjusted for covariates, hazard ratios and 95% CIs of illiteracy versus college education were 2.79 (1.32–5.87) for all‐cause mortality, 3.68 (1.51–8.98) for stroke‐specific mortality, 2.82 (1.20–6.60) for recurrent stroke, and 3.46 (1.50–7.95) for cardiovascular events. The meta‐analysis confirmed the significant association between education status and mortality after stroke (pooled relative risk for lowest versus highest education level, 1.24 [95% CI, 1.05–1.46]).

Conclusions

Low education level was significantly associated with increased risk of mortality, recurrent stroke, and cardiovascular events after ischemic stroke, independently of established risk factors.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT01840072.
V2 and V3 Orders in North-American Icelandic
Authors: Arnbjörnsdóttir Birna , Thráinsson Höskuldur , Nowenstein Iris Edda
Published: August 2020

The finite verb typically occurs in second position in main clauses in Germanic languages other than English. Hence they are often referred to as ʽverb-second languagesʼ or V2-languages for short. The difference between a V2-language and a non-V2 language is shown in (i)–(ii) with Icelandic examples and English glosses (the finite verb is highlighted):

In example (i) the finite verb occurs in second position in Icelandic, immediately following the subject María in Icelandic but in the English gloss it occurs in third position, following the adverb never. In (ii) the finite verb immediately follows the fronted (topicalized) object Maríu in Icelandic but in the English gloss the finite verb again occurs in third position, this time following the subject. This article discusses the influence of intense language contact (English/Icelandic) on the two V2-order types in North American Icelandic (NAmIce), a heritage language spoken in former Icelandic conclaves in North America. We show that the subject-first V2-order is more robust in NAmIce than the topic-first V2-order and less vulnerable to English influence, although both types are affected to some extent. This is interesting for two reasons. First, it has been argued that word order is typically less prone to cross-linguistic influence than for instance morphology. Second, these results suggest that, contrary to common assumption, the two types of V2-orders discussed here may have different syntactic sources in Icelandic syntax.
Word Order in American Danish Declaratives with a Non-Subject Initial Constituent
Authors: Kühl Karoline , Petersen Jan Heegård
Published: August 2020

The paper investigates the placement of subject and finite verb in topicalized, i.e. non-subject initial declarative main clauses in North American Danish. European Danish adheres to the V2-rule and thus requires inversion, while North American Danish allows for non-inversion, i.e. [X]SV word order. Based on a sample of approx. 1700 tokens of topicalized declarative clauses produced by 64 speakers, we observe a general stability of V2 in North American Danish. In order to explain the instances of non-V2, we employ both linguistic and sociolinguistic factors.
Five new genera of angle-wing katydids (Orthoptera: Tettigoniidae: Phaneropterinae: Microcentrini) from the Amazon Rainforest
Authors: DE MELLO MENDES DIEGO MATHEUS , CHAMORRO-RENGIFO JULIANA , RAFAEL JOSÉ ALBERTINO
Published: August 2020

Microcentrini Brunner von Wattenwyl, 1878 is within the subfamily Phaneropterinae and currently comprises 11 genera and 81 species with Neotropical distribution. In this paper, five new genera are described: Boroseiyla gen. nov. (type species Boroseiyla tupeba sp. nov.), Caauara gen. nov. (type species Caauara pinima sp. nov.), Capiguara gen. nov. (type species Capiguara trimaculata sp. nov.), Hyalipenna gen. nov. (type species Hyalipenna tetralineata sp. nov.) and Tuaia gen. nov. (type species Tuaia panacarica sp. nov.) covering a total of seventeen new species registered for the Amazon rainforest. Moreover, Microcentrum nigrolineatum is included in Boroseiyla gen. nov. (Boroseiyla nigrolineatus comb. nov.). Keys to the species of the described genera, maps and observations of natural history are provided.
The psychological impact of COVID-19 on ‘hidden’ frontline healthcare workers
Authors: Teo Winnie Z.Y. , Yap Eng Soo , Yip Christina , Ong Lizhen , Lee Chun-Tsu
Published: August 2020

Background:

The novel coronavirus disease (COVID-19) pandemic has led to rising death tolls and stressed healthcare systems, resulting in an unprecedented psychological stress on healthcare workers worldwide. However, the majority of studies only accounted for frontline healthcare workers with direct patient exposure.

Aim:

This study aims to look at the psychological impact of COVID-19 in a specific, vulnerable and yet hidden group of healthcare workers, namely laboratory healthcare workers who are at high risk exposure to SARS-CoV-2 virus from handling infected patients’ blood samples, in addition to a marked increase in workload.

Method:

A multicentre study was conducted in Singapore via online questionnaire looking at psychological and physical impact of COVID-19 on laboratory healthcare workers. The Generalized Anxiety Disorder 7-item (GAD-7) scale, Zung Self-Rating Depression Scale (SDS) and Numeric rating scale on fear (NRS) were validated scores used in this study. Data analysis was performed using SPSS statistical software version 23 (IBM Corp).

Results:

A total of 122 staffs participated and more than half of the cohort experienced mild to severe fear, anxiety and depression. Increase in depression score was also found to be associated with increased physical exhaustion (OR = 6.1, 95% CI 1.4–29.1, p = .02), loss of appetite (OR = 2.7, 95% CI 1.2–6.0, p = .02), poor sleep quality (OR = 7.5, 95% CI 2.9–19.4, p = .005), and the use of sedative (OR = 3.9, 95% CI 1.1–13.5, p = .03).

Conclusions:

Hence, it is imperative that prompt action needs to be taken to address the psychological needs of this vulnerable group of healthcare workers as the pandemic continues.
Building the Modern State in Developing Countries: Perceptions of Public Safety and (Un)willingness to Pay Taxes in Mexico
Authors: Flores-Macías Gustavo , Sánchez-Talanquer Mariano
Published: August 2020

What is the relationship between taxation and public safety? Contrary to studies suggesting that personal victimization and heightened perceptions of insecurity increase pro-social attitudes and support for state intervention in the form of greater taxation, this article argues that such concerns decrease willingness to pay taxes to address public safety. It estimates what citizens are willing to pay to reduce crime, using an original representative survey conducted in Mexico and relying on the contingent valuation method to assess the value of nonmarket goods. Attitudes toward taxation are found to respond to subjective, sociotropic assessments of public safety rather than to actual risk or occurrences of individual victimization. These findings counter the conventional wisdom that demand for personal security enables greater extraction, a central proposition in classic accounts of state building. Showing that willingness to accept heavier taxation may be weakest among those who perceive the gravest need for security, the study adds precision to theories of fiscal exchange.
Developing the 2020 Diabetes Care & Education Specialist Competencies: A Modified Delphi Study
Authors: Litchman Michelle L. , Ryan Donna , Yehl Kirsten , Rinker Joanne , Burke Sandra Drozdz
Published: August 2020

Purpose

The purpose of the study was to develop diabetes care and education specialty competencies that align with the Association of Diabetes Care & Education Specialists (ADCES).

Method

A Delphi method of consensus development was used, comprising 5 survey rounds. Interprofessional diabetes specialty experts were asked to identify and rate trends and issues important to diabetes specialists on a global scale. Use of a 5-round Delphi process allowed diabetes care and education specialty experts to refine their views considering the progress of the group’s work from round to round.

Results

A total of 457 diabetes care and education specialists across the United States in various professions participated in the Delphi rounds to identify a final set of 130 competencies across 6 domains.

Conclusion

Use of the Delphi method as a consensus guideline helped to identify core competencies for diabetes care and education specialists, reflecting the knowledge and skills necessary to provide evidence-based, high-quality care.
Drug‐Induced Sleep Endoscopy in Pediatric Obstructive Sleep Apnea
Authors: Raposo Diogo , Menezes Marco , Rito João , Trindade‐Soares Mafalda , Adónis Cristina , Loureiro Helena Cristina , Freire Filipe
Published: August 2020

Objective

To describe drug‐induced sleep endoscopy (DISE) findings in children with obstructive sleep apnea and to differentiate them between surgically naïve children and children who had adenotonsillectomy performed.

Study Design

Retrospective case series with chart review.

Setting

Secondary care hospital.

Subjects and Methods

A cohort of 56 children with the diagnosis of obstructive sleep apnea was submitted to DISE and subsequent upper airway surgery: 23 were surgically naïve, and 33 had persistent obstructive sleep apnea after adenotonsillectomy. Comparisons between groups were calculated with chi‐square test and Student’s t test. Simple linear regression was used to model polysomnographic indices.

Results

In surgically naïve children, the most common sites of obstruction were the adenoids (78.2%) and the lateral pharyngeal walls/tonsils (82.6%). In children with persistent obstructive sleep apnea after adenotonsillectomy, the most common sites of obstruction were the adenoids (54.5%), followed by the supraglottis (48.5%) and the tongue base (45.5%). No correlation was found between obstructive apnea‐hypopnea index and DISE findings. Simple linear regression revealed that the degree of obstruction at the tongue base (β = −0.73; 95% CI, −1.22 to −0.25; P =. 004) and the presence of multilevel obstruction (β = −1.75; 95% CI, −3.20 to −0.30; P =. 02) predicted saturation nadir in children with persistent obstructive sleep apnea after adenotonsillectomy.

Conclusion

DISE findings differed between surgically naïve children and children with persistent obstructive sleep apnea after adenotonsillectomy. Increased obstruction at the level of the tongue base and the presence of multilevel obstruction predicted a lower saturation nadir in children with persistent obstructive sleep apnea after adenotonsillectomy.
Screen Time Exposure in Preschool Children with ADHD: A Cross-Sectional Exploratory Study from South India
Authors: Vaidyanathan Sivapriya , Manohar Harshini , Chandrasekaran Venkatesh , Kandasamy Preeti
Published: August 2020

Background:

Concern is mounting regarding screen exposure among young children and its association with mental health. Children with attention deficit hyperactivity disorder (ADHD) may be more vulnerable to its effects such as increased externalizing behaviors and problems with language and cognitive development and biological functions such as sleep. We aimed to assess screen exposure in preschool children with ADHD and to study the correlation of screen time with the severity of ADHD and parental stress levels.

Methods:

Children of age 2.5–6 years, diagnosed with ADHD ( n = 56) were included, and details of the total duration of screen exposure, maximum continuous screen exposure time, and types of screen-based devices used, reasons for screen exposure were collected from primary caregivers. ADHD symptom severity was assessed on Conner's Abbreviated Rating Scale. Family interview for stress and coping, adapted for ADHD, was used to measure parental stress.

Results:

Total screen exposure time in preschool children with ADHD was more than the recommended standards in 80.4% of children, with a median of 140.00 minutes (range: 20–500 minutes). The most commonly used modality was television (98.2%), followed by mobile phones (87.3%), tablets (17.9%), and laptops (10.7%). The severity of ADHD ( r = 0.29, P = 0.02) and parent stress levels ( r = 0.29, P = 0.03) were positively correlated to increased screen time exposure in the child.

Conclusions:

Preschool children with ADHD have screen exposure above the recommended duration of one hour/day. Structured parent training programs for children with preschool ADHD and providing developmentally appropriate interventions are essential in curtailing screen time exposure and also to address parental stress.
Morphological Changes and Cytotoxicity in Isolated Hepatocytes
Authors: Toivola Diana , Eriksson John E.
Published: August 2020

Cells exposed to different types of stress usually exhibit morphological changes. These changes are often referred to as cell blebbing. The aim of this study was to compare a few different cytotoxins acting on freshly isolated rat hepatocytes through different molecular mechanisms. The toxins used were phalloidin and cytochalasin D (for cytoskeletal alterations), menadione (for oxidative stress), the Ca2+-ionophore A23187 (for intracellular Ca2+-elevation) and microcystin-LR (for protein phosphatase inhibition). Light and electron microscopy were used when comparing the morphological effects of the toxins. The morphological effects on microfilaments were studied by labelling F-actin with rhodamine-conjugated phalloidin. The results indicate that, although all the toxins caused cell blebbing, the blebs were morphologically markedly different and the redistribution of actin varied considerably, depending on the toxin used. The modification of the microfilamental architecture seemed to correlate with the morphological changes. Cell blebbing is inevitably a rather vague term for morphological alterations, which may look very different, depending on the subcellular cytotoxic mechanism involved.
Toxicity Testing by Means of Cryopreserved Bovine Spermatozoa
Authors: Kolossa Marike , Seibert Hasso
Published: August 2020

The aim of the present study was to investigate the suitability of bovine spermatozoa cryopreserved in a “defined” medium as an in vitro model for the assessment of the cytotoxic potential of chemicals. The endpoints used for this purpose were motion activity and cellular ATP content. The evaluation of properties of cryopreserved sperm shortly after thawing and at the end of a one-hour incubation period, shows that the cryoprotective medium developed is able to provide suitable cellular material for cytotoxicity tests. Results from experiments employing substances with known modes of action are presented, and suggest that cryopreserved sperm can be used as successfully as native sperm in cytotoxicity tests.
A Bibliometric Evaluation of the Performance of ATLA
Authors: Ungar Krys
Published: August 2020

Analysis of citations to and by ATLA in the years 1988, 1993, 1994 and 1995 show that the impact factor of ATLA has improved significantly over this period, as has the ranking of the journal in relevant sectors of journal publishing. The results further suggest that in vitro toxicology is evolving into a separate discipline and that ATLA is increasingly being seen as one of the key journals for this discipline. However, ATLA's coverage extends beyond in vitro toxicology. It is a vital and unique resource for the promotion of the Three Rs in fields where no other influential specialised journals on alternatives are currently being published.
The Lipopeptide, Pam3Cys-Ser-(Lys)4: An Alternative Adjuvant to Freund's Adjuvant for the Immunisation of Chicken to Produce Egg Yolk Antibodies
Authors: Erhard Michael H. , Schmidt Peter , Hofmann Andrea , Bergmann Josefine , Mittermeier Peter , Kaufmann Pia , Wiesmiiller Karl-Heinz , Bessler Wolfgang G. , Lösch Uli
Published: August 2020

This study describes an alternative adjuvant for the immunisation of chicken. The lipopeptide, Pam3Cys-Ser-(Lys)4 (PCSL), has been demonstrated to be a very potent adjuvant, by immunisation with the hapten methyl phosphonic acid paraaminophenyl 1,2,2-trimethylpropyl diester, with coronavirus, with rotavirus and with the Escherichia coli K99 pilus antigen. The antibody titres in chickens that received PCSL were compared with those in animals that received Freund's complete adjuvant/Freund's incomplete adjuvant (FCA/FIA). Antigen-dependent differences in antibody titres could be shown. The optimal dosage for PCSL was 250μg per injection. Whereas injection of FCA/FIA resulted in chronic inflammatory alterations, mostly accompanied with granulomatous reactions, no long-term tissue damage could be found with PCSL. When PCSL was used as the adjuvant, the total immunoglobulin Y (IgY) levels in chicken sera were constant during the immunisation period (20.2mg/ml, SD ± 1.3), and were significantly different (p < 0.0001) from those in chickens given FCA as adjuvant (26.6mg7ml, SD ± 4.9). IgY concentrations in the egg yolks showed no significant differences in both groups (PCSL — 13.7mg/ml, SD ± 3.7; FCA — 13.5mg/ml, SD ± 4.2), and were significantly lower (p < 0.0001) than the IgY serum levels.
Mechanism of Tamoxifen's Retinal Toxicity, Studied in Pig Pigment Epithelial Cell Cultures
Authors: Mäenpää Hanna , Toimela Tarja , Saransaari Pirjo , Salminen Lotta , Tähti Hanna
Published: August 2020

The anticancer drug tamoxifen is widely used in breast cancer therapy. Tamoxifen has been reported to cause ocular toxicity and impairment of vision in epidemiological studies. To study the possible role of an excitotoxic mechanism in the ocular toxicity of tamoxifen, we investigated the effect of tamoxifen on retinal pigment epithelium (RPE) glutamate uptake in vitro. RPE, a layer of cells between photoreceptors and choroidal capillaries, contributes to the regulation of the concentration of the major excitatory amino acid, glutamate, in the sub-retinal space. Dysfunction in RPE glutamate uptake can lead to accumulation of extracellular glutamate and can cause various excitotoxic effects in the retina. The study was conducted by using cultured pig RPE cells. Six different tamoxifen citrate concentrations, ranging from lμM to 100μM, and [3H]-L-glutamate were added to the culture medium. To specify the glutamate uptake, 1mM dinitrophenol was added and a Na+-free culture was used. Due to the anti-oestrogenic character of tamoxifen, the possible effect of β-oestradiol on the glutamate uptake of RPE was also examined. The results show that glutamate uptake by RPE cells was reduced in the presence of tamoxifen, and that the reduction was dose-dependent. These results suggest that tamoxifen exposure could lead to the extracellular accumulation of glutamate. Disturbances in glutamate uptake can cause eye toxicity via an excitotoxic mechanism. The glutamate uptake of RPE cells was reduced under Na+-free conditions and was also reduced in the presence of dinitrophenol.
Automated in Vitro Dermal Absorption (AIVDA): A New in Vitro Method for Investigating Transdermal Flux
Authors: Moody Richard P.
Published: August 2020

A new in vitro method for investigating transdermal flux is described. The method, called Automated In Vitro Dermal Absorption (AIVDA), employed small autosampler vial inserts (Moody cells) to hold human skin (0.07cm2) in a standard autosampler carousel. HPLC was used to monitor the permeation rate of test compounds. Analysis was fully automated and remotely monitored and controlled via a modem. A modified Hank's balanced salt solution was used to minimise HPLC background interference. Permeation assays conducted with Deep Woods®, a commercial N,N-diethyl-m-toluamide (DEET)-based mosquito repellent, showed no significant difference in DEET absorption between fresh and frozen human abdominal skin (Student's t test [p ≤ 0.05] 56 ± 9.1% [n = 4] and 48 ± 6.3% [n = 4], respectively). No significant difference was obtained for DEET absorption in human skin pretreated with barrier cream. Preliminary tests conducted to validate AIVDA versus the standard Bronaugh procedure demonstrated excellent agreement for DEET permeation in rat skin (62 ± 12.8% [n = 4] Moody cells; 59 ± 8.1% [n = 3] Bronaugh cells). AIVDA has many advantages over other in vitro permeation tests, including automation, higher analytical sensitivity, rapid sample processing and the ability to use small (5mm outside diameter) skin specimens.
The Validation of Toxicological Prediction Models
Authors: Archer Graeme , Balls Michael , Bruner Leon H. , Curren Rodger D. , Fentem Julia H. , Holzhütter Hermann-Georg , Liebsch Manfred , Lovell David P. , Southee Jacqueline A.
Published: August 2020

An alternative method is shown to consist of two parts: the test system itself; and a prediction model for converting in vitro endpoints into predictions of in vivo toxicity. For the alternative method to be relevant and reliable, it is important that its prediction model component is of high predictive power and is sufficiently robust against sources of data variability. In other words, the prediction model must be subjected to criticism, leading successful models to the state of confirmation. It is shown that there are certain circumstances in which a new prediction model may be introduced without the necessity to generate new test system data.
Reduction of the New Tetrazolium Dye, Alamar Blue™, in Cultured Rat Hepatocytes and Liver Fractions
Authors: Andrews Mark J. , Garle Michael J. , Clothier Richard H.
Published: August 2020

Alamar Blue™ (AB) is a new tetrazolium dye substrate that has been introduced as an alternative cell viability indicator. AB is reduced by intracellular reductases to a product which is exported from cells and can be quantified by fluorescent or spectrophotometric methods. We investigated the processes by which AB was reduced in liver cytosolic, microsomal or mitochondrial fractions and in cultured rat hepatocytes. AB reduction was catalysed by all liver fractions in an NADPH-dependent and NADH-dependent manner; the cytosolic fraction catalysed the highest rate of AB reduction. All of these activities were inhibited by dicoumarol (10μM), except AB reduction catalysed by NADH in mitochondrial fractions, which was resistant to the effects of dicoumarol and the metabolic inhibitors, but sensitive to inhibition by mercury (II) chloride. In hepatocyte cultures, AB reduction was stimulated by dicoumarol (10μM), menadione (10μM), rotenone (10μM), lactate (1–10mM) and fluoride (3-10mM). Potassium cyanide, ethanol and malonate had little effect. The results from this study suggest that AB is reduced in an NADPH-quinone oxidoreductase-dependent fashion, but that superoxide may also be involved in the reduction of AB. The modulation of AB reduction by lactate means that AB reduction may be modified by alterations in intermediary metabolism which are not a reflection of cell lethality. Therefore, great care should be exercised when using AB reduction as a viability indicator.
Responses of Glutathione S-transferase and Glutathione Peroxidases to Feeding Rate of a Wolf Spider Pardosa prativaga
Authors: Nielsen Søren Achim , Toft Søren
Published: August 2020

Groups of large juvenile wolf spiders ( Pardosa prativaga) were kept on constant Drosophila melanogaster rations of 0 (starvation), 1, 2, 3.5, 7, 14 or 28 flies per week, or ad libitum feeding. After 3–4 weeks, they were sacrificed and the activities of three biomarker enzyme systems — glutathione S-transferase (GST) with chlorodinitrobenzene as substrate, glutathione peroxidase with H2O2 as substrate (GSH-Px[H2O2]), or glutathione peroxidase with t-butyl-hydroperoxide as substrate (GSH-Px[TBH]) — were assayed. Two systems (GST and GSH-Px[H2O2]) showed decreasing enzyme activity with increasing feeding rate, whereas the variation in GSH-Px(TBH) was independent of feeding rate. Sex and body weight had no influence on enzyme activity.
Monitoring Method as a Basis for Need-based Control of Varroa Mites (Varroa jacobsoni) Infesting Honey Bee (Apis mellifera) Colonies
Authors: Brødsgaard Camilla J. , Brødsgaard Henrik F.
Published: August 2020

To avoid excessive use of pesticides in controlling varroa mites (Varroa jacobsoni) in honey bee (Apis mellifera) colonies, a method for monitoring the population size of the mites was developed. The relationship between the size of mite populations (y) in full-size honey bee colonies and natural mite mortality, measured as the number of mites falling on plastic inserts (drop-down), was investigated in Danish apiaries. The results suggest that a straight linear model (y = + x) describes the relationship between the mite population present in a colony and the calculated daily number of naturally dead mites collected on inserts during either 1-week or 3-week periods before sampling. The parameters of the straight line relationship between the population size and the daily mite drop-down during a 1-week period are: β = 0.0069 and α = -1.858 ( r2 = 0.77, p < 0.0001). For a 3-week period, the parameters are: β = 0.0063 and α = -0.403 ( r 2 = 0.83, p < 0.0001). If the model input is adjusted for the brood-rearing pattern of the sampled colonies, i.e. colonies with capped brood cells covering less than one side of a comb in total (2800–3200 cells) are excluded from the input, the fit of the model is improved. In this case, the parameters for the 1-week sampling period are: β = 0.0075 and α = -1.184 ( r2 = 0.88, p < 0.0001), and the parameters for the 3-week sampling period are: β = 0.0071 and α = -0.864 ( r2 = 0.91, p < 0.0001).
The Use of Simultaneous Fluorescence and Differential Phase Confocal Microscopy to Study Alamar Blue™ Reduction in an Epithelial Cell Line
Authors: Garside John R. , Clothier Richard H. , Somekh Mike G. , See Chung Wah
Published: August 2020

The Alamar Blue™ reduction assay is used as an indicator of cellular viability in in vitro tests for the prediction of ocular irritancy. Alamar Blue itself has a low cytotoxicity, so repeat exposure and recovery studies can be performed on the same cells. This paper contains the results of a preliminary investigation of interactions between the Alamar Blue dye and a confluent monolayer of epithelial Madin-Darby canine kidney cells. This was performed by using an experimental fluorescence microscope and differential phase confocal microscope designed for studying live samples in vitro. The initiation of Alamar Blue reduction to its fluorescent product did not occur at the same time in all cells, but started in a small number and spread progressively through their immediate neighbours. There was clear localisation of the reduced (fluorescent) Alamar Blue within the nuclei and other organelles.
Comparative Evaluation of In Vitro and In Vivo Assays for the Detection of Avian Infectious Bronchitis Virus as a Contaminant of Live Poultry Vaccines
Authors: Falcone Emiliana , Vignolo Edoardo , Di Trani Livia , Puzelli Simona , Tollis Maria
Published: August 2020

A reverse transcriptase polymerase chain reaction (RT-PCR) assay specific for identifying avian infectious bronchitis virus (IBV) in poultry vaccines, and the serological response to IBV induced by the inoculation of chicks with a Newcastle disease vaccine spiked with the Massachusetts strain of IBV, were compared for their ability to detect IBV as a contaminant of avian vaccines. The sensitivity of the IBV-RT-PCR assay provided results which were at least equivalent to the biological effect produced by the inoculation of chicks, allowing this assay to be considered a valid alternative to animal testing in the quality control of avian immunologicals. This procedure can easily be adapted to detect a number of contaminants for which the in vivo test still represents the only available method of detection.
A Germination Bioassay as a Toxicological Screening System for Studying the Effects of Potential Prodrugs of Naproxen
Authors: la Parra Mario Gonzalez-de , Ramos-Mundo Carlos , Jimenez-Estrada Manuel , Leon Claudia Ponce-de , Castillo R. , Tejeda Veronica , Cuevas Karla G. , Enriquez Raul G.
Published: August 2020

A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only ( R)-(+)-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthale-neacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus.
A Study on UV Filter Chemicals from Annex VII of European Union Directive 76/768/EEC, in the In Vitro 3T3 NRU Phototoxicity Test
Authors: Spielmann Horst , Balls Michael , Dupuis Jack , Pape Wolfgang J. W. , de Silva Odile , Holzhütter Hermann-Georg , Gerberick Frank , Liebsch Manfred , Lovell Will W. , Pfannenbecker Uwe
Published: August 2020

In 1996, the Scientific Committee on Cosmetology of DGXXIV of the European Commission asked the European Centre for the Validation of Alternative Methods to test eight UV filter chemicals from the 1995 edition of Annex VII of Directive 76/768/EEC in a blind trial in the in vitro 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) test, which had been scientifically validated between 1992 and 1996. Since all the UV filter chemicals on the positive list of EU Directive 76/768/EEC have been shown not to be phototoxic in vivo in humans under use conditions, only negative effects would be expected in the 3T3 NRU PT test. To balance the number of positive and negative chemicals, ten phototoxic and ten non-phototoxic chemicals were tested under blind conditions in four laboratories. Moreover, to assess the optimum concentration range for testing, information was provided on appropriate solvents and on the solubility of the coded chemicals. In this study, the phototoxic potential of test chemicals was evaluated in a prediction model in which either the Photoirritation Factor (PIF) or the Mean Photo Effect (MPE) were determined. The results obtained with both PIF and MPE were highly reproducible in the four laboratories, and the correlation between in vitro and in vivo data was almost perfect. All the phototoxic test chemicals provided a positive result at concentrations of 1μg/ml, while nine of the ten non-phototoxic chemicals gave clear negative results, even at the highest test concentrations. One of the UV filter chemicals gave positive results in three of the four laboratories only at concentrations greater than 100μg/ml; the other laboratory correctly identified all 20 of the test chemicals. An analysis of the impact that exposure concentrations had on the performance of the test revealed that the optimum concentration range in the 3T3 NRU PT test for determining the phototoxic potential of chemicals is between 0.1μg/ml and 10μg/ml, and that false positive results can be obtained at concentrations greater than 100μg/ml. Therefore, the positive results obtained with some of the UV filter chemicals only at concentrations greater than 100μg/ml do not indicate a phototoxic potential in vivo. When this information was taken into account during calculation of the overall predictivity of the 3T3 NRU PT test in the present study, an almost perfect correlation of in vitro versus in vivo results was obtained (between 95% and 100%), when either PIF or MPE were used to predict the phototoxic potential. The management team and participants therefore conclude that the 3T3 NRU PT test is a valid test for correctly assessing the phototoxic potential of UV filter chemicals, if the defined concentration limits are taken into account.
MEIC Evaluation of Acute Systemic Toxicity
Authors: Ekwall Björn , Clemedson Cecilia , Crafoord Balcarras , Ekwall Barbro , Hallander Sara , Walum Erik , Bondesson Inger
Published: August 2020

The Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme was set up to evaluate the relevance for acute human systemic toxicity of in vitro cytotoxicity tests. At the end of the programme in the summer of 1996, 29 laboratories had tested all 50 reference chemicals in 61 cytotoxicity assays. As a necessary prerequisite to the forthcoming evaluation papers of this series, this paper presents the animal and human toxicity data of the programme. This database contains tabulated handbook data for the 50 chemicals, on: a) oral rat and mouse LD50 values; b) acute oral lethal doses in humans; c) clinically measured acute lethal serum concentrations in humans; d) acute lethal blood concentrations in humans measured postmortem; e) peaks from curves of an approximate 50% lethal blood/serum concentration over time after ingestion (LC50 curves), derived from a compilation of human acute poisoning case reports; f) human kinetics of single doses, including absorption, peak time, distribution/elimination curve, plasma half-life, distribution volume, distribution to organs (notably brain), and blood protein binding; and g) qualitative human acute toxicity data, including lethal symptoms, main causes of death, average time to death, target organs, presence of histopathological injury in target organs, presence of toxic metabolites, and known or hypothetical mechanisms for the lethal toxicity. The rationales for selection of the human toxicity data are also noted. The methods used to compile the in vivo toxicity data are described, including a presentation of a new method of constructing LC50 curves. Finally, the merits and shortcomings of the various human toxicity data for evaluation purposes are discussed.
The Law, Psychology, and the Criminal (Ii)
Authors: Guest E. R.
Published: August 2020

[This is the final part of an address the first part of which appeared in our last issue. It was delivered to the Romilly Association at Reading and is reproduced here by permission of that Association and of Mr. Guest. In the first instalment Mr. Guest criticised the excessive use of psychiatry and ended his article with a quotation from Mr. Basil Henriques’ book, “Indiscretions of a Magistrate,” which, after describing the report of one psychiatrist on a case before his Court, said “ We were not greatly impressed, nor were we very much helped in dealing with the case.”]
Yangxin granules alleviate doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis mediated by AKT/GSK3β/β-catenin signaling
Authors: Ren Dezhi , Li Fang , Cao Qingwen , Gao An , Ai Yingna , Zhang Junru
Published: August 2020

Background

Yangxin granules (YXC), a Chinese herbal medicine, have been confirmed to have clinical benefits in the treatment of heart failure. This study examined the effects and molecular mechanisms of YXC in the treatment of doxorubicin-induced cardiotoxicity in vitro.

Methods

H9c2 cardiomyocytes were pretreated with YXC (5, 10, or 20 mg/mL) or the AKT inhibitor MK-2206 (50 nM) before doxorubicin treatment (1 µM). Cell apoptosis, viability, inflammatory factor expression (TNF-α, IL-1β, and IL-6), and oxidative stress mediator levels including superoxide dismutase, reactive oxygen species, and malondialdehyde were detected.

Results

YXC increased the viability of H9c2 cells. In addition, doxorubicin inhibited AKT/GSK3β/β-catenin signaling, whereas YXC increased the expression of phosphorylated AKT and GSK3β, and β-catenin in doxorubicin-treated H9c2 cells. Moreover, T-cell factor/lymphoid enhancer factor signaling downstream of β-catenin was also activated by YXC. YXC pretreatment also inhibited doxorubicin-induced inflammation, oxidative stress, and apoptosis. However, MK-2206 reversed the effects of YXC in doxorubicin-treated H9c2 cells.

Conclusions

YXC alleviates doxorubicin-induced inflammation, oxidative stress, and apoptosis in H9c2 cells. These effects might be mediated by the AKT/GSK3β/β-catenin signaling pathway. YXC might have preventive effects against doxorubicin-induced heart failure.
Role of low-molecular-weight heparin in altering uterine artery blood flow in recurrent spontaneous abortion: a prospective study
Authors: Zhang Kemei , Wang Ensheng , Li Yang , Xu Haiyan , Zhang Jiaou , Wang Xuhong , Shu Jing
Published: August 2020

Objective

This study aimed to determine the role of uterine artery blood flow (UABF) in recurrent spontaneous abortion (RSA) and to determine a viable option to promote the outcome of pregnancy.

Methods

A total of 421 women were prospectively recruited for this research. UABF indices, including the systolic/diastolic ratio, pulsatility index and resistance index, during the midluteal phase were compared between patients with RSA and women without RSA (controls). After low-molecular-weight heparin (LMWH) was administered to patients with RSA, indices at 7, 10, and 12 weeks of gestation were compared between the two groups.

Results

UABF indices during the midluteal phase were significantly higher in the RSA group than in the control group. After LMWH was administered to the RSA group, UABF indices in the first trimester were similar to those in the control group. The rate of spontaneous miscarriage was also similar between the groups after LMWH treatment.

Conclusions

Our study shows that sufficient uterine perfusion is crucial for a successful pregnancy. LMWH reduces the rate of spontaneous miscarriage in patients with RSA to a similar rate in women without RSA. LMWH might play a role in decreasing UABF resistance and increasing uterine perfusion.
“Just-in-Place” labor: Driver organizing in the Uber workplace
Authors: Wells Katie J , Attoh Kafui , Cullen Declan
Published: August 2020

This paper examines the socio-spatial dynamics of worker agency in the platform economy in the Washington, D.C. region. Drawing on the field of labor geography, we document the collective and inherently spatial conditions of laboring under and through new technologies for three years prior to, and six months after, a strike by Uber drivers in May 2019. In doing so, we explore what Uber’s platform means for the production, accumulation, and contestation of power. We argue that the big innovation of this platform is the creation of a “just-in-place” worker. Akin to those materials for assembly lines that arrived just-in-time for production, so too do drivers end up in just the right place for Uber’s services to be offered. We also argue that Uber’s attempts to keep its workers “just-in-place,” which generally isolate and disempower drivers, can actually enable new modes of organization. At a D.C. airport, drivers who were emplaced in a parking lot overcame one of the fundamental conditions of the Uber workplace: socio-spatial atomization. The airport became a space in which the “just-in-place” worker could, at least for a time, challenge such emplacement and exercise a form of collective worker agency by re-working Uber’s dynamic pricing system.