bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of In Vitro COPD Models for Tobacco Regulatory Science: Workshop Proceedings, Conclusions and Paths Forward for In Vitro Model Use
Authors: Behrsing Holger , Raabe Hans , Manuppello Joseph , Bombick Betsy , Curren Rodger , Sullivan Kristie , Sethi Sanjay , Phipps Richard , Tesfaigzi Yohannes , Yan Sherwin , D'Ruiz Carl , Tarran Robert , Constant Samuel , Phillips Gary , Gaça Marianna , Hayden Patrick , Cao Xuefei , Mathis Carole , Hoeng Julia , Braun Armin , Hill Erin
Published: April 2019

The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed ‘modified risk’. On 8–10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide.
Evaluation of an In Vitro Cell Culture Assay for the Potency Assessment of Recombinant Human Erythropoietin
Authors: Machado Francine T. , Maldaner Fernanda P.S. , Perobelli Rafaela F. , Xavier Bruna , da Silva Francielle S. , de Freitas Guilherme W. , Bartolini Paolo , Ribela Maria Tereza C.P. , Dalmora Sérgio L.
Published: April 2019

Recombinant human erythropoietin is a sialoglycoprotein that stimulates erythropoiesis. To assess potency of human erythropoietin produced by recombinant technology, we investigated an in vitro TF-1 cell proliferation assay, which was applied in conjunction with a reversed-phase liquid chromatography method for the determination of the content of sialic acids. The results obtained, which were higher than 126.8ng/μg, were compared with those obtained with the in vivo normocythaemic mouse bioassay. The in vitro assay resulted in a non-significant lower mean difference of the estimated potencies (0.61% ± 0.026, p > 0.05). The use of this combination of methods represents an advance toward the establishment of alternative in vitro approaches, in the context of the Three Rs, for the potency assessment of biotechnology-derived medicines.
Statistics of Scientific Procedures on Living Animals Great Britain 2015 — Highlighting an Ongoing Upward Trend in Animal Use and Missed Opportunities for Reduction
Authors: Hudson-Shore Michelle
Published: April 2019

The Annual Statistics of Scientific Procedures on Living Animals Great Britain 2015 indicate that the Home Office were correct in recommending that caution should be exercised when interpreting the 2014 data as an apparent decline in animal experiments. The 2015 report shows that, as the changes to the format of the annual statistics have become more familiar and less problematic, there has been a re-emergence of the upward trend in animal research and testing in Great Britain. The 2015 statistics report an increase in animal procedures (up to 4,142,631) and in the number of animals used (up to 4,069,349). This represents 1% more than the totals in 2013, and a 7% increase on the procedures reported in 2014. This paper details an analysis of these most recent statistics, providing information on overall animal use and highlighting specific issues associated with genetically-altered animals, dogs and primates. It also reflects on areas of the new format that have previously been highlighted as being problematic, and concludes with a discussion about the use of animals in regulatory research and testing, and how there are significant missed opportunities for replacing some of the animal-based tests in this area.
In Vitro Human Tissues via Multi-material 3-D Bioprinting
Authors: Kolesky David B. , Homan Kimberly A. , Skylar-Scott Mark , Lewis Jennifer A.
Published: April 2019

This paper highlights the foundational research on multi-material 3-D bioprinting of human tissues, for which the Lewis Bioprinting team at Harvard University was awarded the 2017 Lush Science Prize. The team's bioprinting platform enables the rapid fabrication of 3-D human tissues that contain all of the essential components found in their in vivo counterparts: cells, vasculature (or other tubular features) and extracellular matrix. The printed 3-D tissues are housed within a customised perfusion system and are subjected to controlled microphysiological environments over long durations (days to months). As exemplars, the team created a thick, stem cell-laden vascularised tissue that was controllably differentiated toward an osteogenic lineage in situ, and a 3-D kidney tissue that recapitulated the proximal tubule, a sub-unit of the nephron responsible for solute reabsorption. This highly versatile platform for manufacturing 3D human tissue in vitro opens new avenues for replacing animal models used to develop next-generation therapies, test toxicity and study disease pathology.
2017 Lush Science Prize
Authors: McCann Jenny , McCann Terry
Published: April 2019

Now in its sixth year, the Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In the event of a major breakthrough leading to the replacement of animal tests in the area of 21st Century Toxicology, a Black Box Prize (equivalent to the entire annual fund) is awarded. The Science Prize is awarded to the researchers whose work the judging panel believe has made the most significant contribution to the replacement of animal testing in the preceding year. This Background Paper outlines the research projects that were shortlisted and presented to the judging panel as potential candidates for the 2017 Lush Science Prize. This process involved reviewing recent work of the relevant scientific institutions and projects in this area, such as the OECD, Human Toxome Project, UK NC3Rs, US Tox21 programme, ToxCast programme and the Human Toxicology Project Consortium. Recent developments in toxicity testing research were also identified by searching for relevant published papers in the literature, and analysing abstracts from conferences focusing on animal replacement in toxicity testing that had been held in the preceding 12 months — for example, the 2016 EUSAAT-Linz conference and the 2017 Society of Toxicology annual conference.
In Vitro Alternatives and Phototoxicity Testing. I. Evaluation of In Vitro Phototoxicity Assays
Authors: Okamoto Yuuko , Ryu Akemi , Ohkoshi Kenji
Published: April 2019

Three in vitro phototoxicity assays — the photohaemolysis assay, the haemoglobin (Hb) photo-oxidation assay, and the 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) assay — were evaluated for use as screening methods in predicting the phototoxicity of test substances. Twenty-seven test substances, including cosmetic ingredients and drugs, were assessed in this study. The phototoxicity predicted in each assay was compared with that in guinea-pigs. In total, nine phototoxic substances used in this study could be detected by some of the in vitro phototoxicity assays. Eleven test substances regarded as non-phototoxic in vivo were predicted as non-phototoxic in the in vitro assays. Of the eight false positives revealed in some of the in vitro assays, five are believed to be photo-allergens. This suggests that in vitro phototoxicity assays might not be able to discriminate clearly between in vivo phototoxicity and in vivo photo-allergy, because the mechanisms in both processes are based on photodynamic reactions. The predictability of the three in vitro assays was comparatively good, but positive predictive values were low. The equivalence values of the photohaemolysis assay, the Hb photo-oxidation assay and the 3T3 NRU PT assay were 81%, 70% and 70%, respectively. From these results, we suggest that the three in vitro phototoxicity assays could be used as screens in predicting phototoxicity.
In Vitro Alternatives and Phototoxicity Testing. II. Effects of Reactive Oxygen Species in In Vitro Phototoxicity Assays
Authors: Okamoto Yuuko , Ryu Akemi , Ohkoshi Kenji
Published: April 2019

The effects of reactive oxygen species (including singlet oxygen) in two in vitro phototoxicity assays — the 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) assay and the photohaemolysis assay — were assessed by using scavengers. Fifteen test substances, which had previously been shown to be phototoxic in vitro, were assessed. Eleven of these produced singlet oxygen. The major factor in the photodynamic reaction of bithionol was thought to be a Type I reaction, because bithionol did not produce singlet oxygen and did not react to histidine. Acridine was regarded as a Type II substance, because of the evident effect of histidine as a scavenger. 8-Methoxypsoralen and 5-methoxypsoralen produced singlet oxygen, but their actions were not affected by the scavengers. In this study, we confirmed that reactive oxygen species have great effects in in vitro phototoxicity, and that the 3T3 NRU PT assay can be used to detect effects which are thought to be the direct reaction of an excited photosensitiser to biological substrates (Type III reaction), for example, 8-methoxypsoralen. Therefore, we suggest that photohaemolysis and phototoxicity could be used to evaluate the photodynamic mechanisms of photosensitising chemicals.
Learning curve for multidisciplinary team setup in veno-venous extracorporeal membrane oxygenation for acute respiratory failure
Authors: Yeo Hye Ju , Cho Woo Hyun , Kim Dohyung
Published: April 2019

Background:

Quality control is essential for a successful extracorporeal membrane oxygenation program. We investigated the learning curve for outcome improvement and focused on factors associated with failure of extracorporeal membrane oxygenation treatment.

Methods:

Between August 2011 and May 2017, 150 patients were supported with veno-venous extracorporeal membrane oxygenation for acute respiratory failure. The learning curve was examined using cumulative sum analysis. We defined successful extracorporeal membrane oxygenation treatment as intensive care unit discharge, acceptable failure rate as 40%, and unacceptable failure rate as 60%. We chronologically divided patients into three periods with 50 consecutive patients each and retrospectively compared the clinical outcomes by period.

Results:

Overall, weaning and survival to discharge rates were 72.7% and 56%, respectively. Cumulative sum analysis indicated that the extracorporeal membrane oxygenation team achieved nearly acceptable performance after 56 cases and consistently acceptable performance after 104 cases. Clinical outcomes were improved by period: weaning rate (58% vs. 80% vs. 80%, p = 0.017); intensive care unit discharge rate (42% vs. 60% vs. 78%, p = 0.001); survival to discharge rate (40% vs. 58% vs. 70%, p = 0.010); and 1 year survival rate (40% vs. 56% vs. 70%, p = 0.010). In multivariate analysis, infection (odds ratio: 4.54, 95% confidence interval: 1.83-11.27, p = 0.001), immune compromise (odds ratio: 5.78, 95% confidence interval: 1.66-20.14, p = 0.006), extracorporeal membrane oxygenation team period (odds ratio: 2.12, 95% confidence interval: 1.14-3.92, p = 0.017), and age (odds ratio: 1.09, 95% confidence interval: 1.05-1.14, p < 0.001) were associated with extracorporeal membrane oxygenation failure.

Conclusion:

More than 100 cases of extracorporeal membrane oxygenation experience were necessary for acceptable performance and stabilization of outcomes.
Long-term pulmonary function and quality of life in adults after extracorporeal membrane oxygenation for respiratory failure
Authors: von Bahr Viktor , Kalzén Håkan , Frenckner Björn , Hultman Jan , Frisén K Gunilla , Lidegran Marika K , Diaz Sandra , Malfertheiner Maximilian V , Millar Jonathan E , Dobrosavljevic Tanja , Eksborg Staffan , Holzgraefe Bernhard
Published: April 2019

Background:

There is a significant long-term burden on survivors after acute respiratory distress syndrome, even 5 years after discharge. This is not well investigated in patients treated with extracorporeal membrane oxygenation. The objective of this study was to describe very-long-term (⩾3 years) disability in lung function and morphology, quality of life, mood disorders, walking capacity, and return to work status in extracorporeal membrane oxygenation survivors.

Methods:

Single-center retrospective cohort study on long-term survivors treated with extracorporeal membrane oxygenation for respiratory failure between 1995 and 2010 at a tertiary referral center in Sweden. Eligible patients were approached, and those who consented were interviewed and investigated during a day at the hospital.

Results:

A total of 38 patients were investigated with a median follow-up time of 9.0 years. Quality of life was reduced in several Short form 36 (SF-36) subscales and all domains of the St George’s Respiratory Questionnaire, similar to previous studies in conventionally managed acute respiratory distress syndrome survivors. A reduced diffusion capacity of carbon monoxide was seen in 47% of patients, and some degree of residual lung parenchymal pathology was seen in 82%. Parenchymal pathology correlated with reductions in quality of life and diffusion capacity. Symptoms of anxiety and depression were seen in 22% and 14%, respectively.

Conclusion:

A significant long-term burden remains even 3–17 years after extracorporeal membrane oxygenation treatment, similar to conventionally managed acute respiratory distress syndrome survivors. Future prospective studies are needed to elucidate risk factors for these sequelae.
Hemoglobin trigger and approach to red blood cell transfusions during veno-venous extracorporeal membrane oxygenation: the international TRAIN-ECMO survey
Authors: Martucci Gennaro , Grasselli Giacomo , Tanaka Kenichi , Tuzzolino Fabio , Panarello Giovanna , Schmidt Matthieu , Bellani Giacomo , Arcadipane Antonio
Published: April 2019

Introduction:

Optimal red blood cell transfusion practice during veno-venous extracorporeal membrane oxygenation (VV ECMO) is still under debate. This survey aimed to assess the Hb trigger (also comparing with other critically ill patients) and major physiologic determinants considered for transfusions during veno-venous extracorporeal membrane oxygenation.

Methods:

Voluntary Web-based survey, endorsed by the European Society of Intensive Care Medicine, conducted among VV ECMO pratictioners worldwide.

Results:

A total of 447 respondents worldwide answered the questionnaire: 277 (61.9%) from Europe, 99 (22.1%) from North America, 36 (8.2%) from Asia and Oceania, and 35 (7.8%) from Central and South America. Among the respondents, 59.2% managed less than 12 venous extracorporeal membrane oxygenation runs/year, 19.4% between 12 and 24 runs/year, and 21.4% more than 24 runs/year. Of the respondents, 54.4% do not use a predefined Hb trigger in veno-venous extracorporeal membrane oxygenation, and, while the rate of adoption of a defined trigger varied worldwide, the effective value of Hb did not differ significantly among macro-regions. In patients on veno-venous extracorporeal membrane oxygenation, the Hb trigger to initiate red blood cell transfusion, was higher than in other critically ill patients: 9.1 ± 1.8 g/dL versus 8.3 ± 1.7 g/dL, p < 0.01. The Hb trigger was lower in centers with more than 24 venous extracorporeal membrane oxygenation runs/year (8.4 mg/dL (95% CI: 7.7-8.9)); (8.9 mg/dL (95% CI: 8.2-9.7)) in centers with between 12 and 24 venous extracorporeal membrane oxygenation runs/year; and (9.6 mg/dL (95% CI: 9.1-10.0)) in centers with fewer than 12 venous extracorporeal membrane oxygenation runs/year (p < 0.01). Several and variable adjunctive parameters are considered in cases of uncertainty for transfusion: the principal are hemodynamic status, SvO2, lactates, and fluid balance.

Conclusion:

Although the use of a predefined Hb trigger is still under-adopted among centers with low or median extracorporeal membrane oxygenation case volume, the majority of respondents use a higher Hb trigger for veno-venous extracorporeal membrane oxygenation patients compared with other critically ill patients. Higher volume centers tolerate lower Hb levels.
Management of accidental hypothermia: an established extracorporeal membrane oxygenation centre experience
Authors: Balik Martin , Porizka Michal , Matousek Vojtech , Brestovansky Petr , Svobodova Eva , Flaksa Marek , Rulisek Jan , Mlejnsky Frantisek , Hodkova Gabriela , Grus Tomas , Vobruba Vaclav , Belohlavek Jan
Published: April 2019

Introduction:

Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce.

Methods:

A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively.

Results:

A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non–extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non–extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non–extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1.

Conclusion:

Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.
Mesenchymal stem cells may ameliorate inflammation in an ex vivo model of extracorporeal membrane oxygenation
Authors: von Bahr Viktor , Millar Jonathan E , Malfertheiner Maximillian V , Ki Katrina K , Passmore Margaret R , Bartnikowski Nicole , Redd Meredith A , Cavaye Michael , Suen Jacky Y , McAuley Danny F , Fraser John F
Published: April 2019

Introduction:

Mesenchymal stem cells exhibit immunomodulatory properties which are currently being investigated as a novel treatment option for Acute Respiratory Distress Syndrome. However, the feasibility and efficacy of mesenchymal stem cell therapy in the setting of extracorporeal membrane oxygenation is poorly understood. This study aimed to characterise markers of innate immune activation in response to mesenchymal stem cells during an ex vivo simulation of extracorporeal membrane oxygenation.

Methods:

Ex vivo extracorporeal membrane oxygenation simulations (n = 10) were conducted using a commercial extracorporeal circuit with a CO2-enhanced fresh gas supply and donor human whole blood. Heparinised circuits (n = 4) were injected with 40 × 106-induced pluripotent stem cell–derived human mesenchymal stem cells, while the remainder (n = 6) acted as controls. Simulations were maintained, under physiological conditions, for 240 minutes. Circuits were sampled at 15, 30, 60, 120 and 240 minutes and assessed for levels of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumour necrosis factor-α, transforming growth factor-β1, myeloperoxidase and α-Defensin-1. In addition, haemoglobin, platelet and leukocyte counts were performed.

Results:

There was a trend towards reduced levels of pro-inflammatory cytokines in mesenchymal stem cell–treated circuits and a significant increase in transforming growth factor-β1. Blood cells and markers of neutrophil activation were reduced in mesenchymal stem cell circuits during the length of the simulation. As previously reported, the addition of mesenchymal stem cells resulted in a reduction of flow and increased trans-oxygenator pressures in comparison to controls.

Conclusions:

The addition of mesenchymal stem cells during extracorporeal membrane oxygenation may cause an increase in transforming growth factor-β1. This is despite their ability to adhere to the membrane oxygenator. Further studies are required to confirm these findings.
Good end-of-life care in nursing home according to the family carers’ perspective: A systematic review of qualitative findings
Authors: Gonella Silvia , Basso Ines , De Marinis Maria Grazia , Campagna Sara , Di Giulio Paola
Published: April 2019

Background:

Nursing homes are becoming a common site where delivering end-of-life care for older adults. They often represent the junction between the curative and the palliative phase.

Aim:

To identify the elements that nursing home residents’ family carers perceive as good end-of-life care and develop a conceptual model of good end-of-life care according to the family perspective.

Design:

Systematic review (PROSPERO no. 95581) with meta-aggregation method.

Data Sources:

Five electronic databases were searched from inception between April and May 2018. Published qualitative studies (and mixed-method designs) of end-of-life care experience of nursing home family carers whose relative was dead or at the end-of-life were included. No language or temporal limits were applied.

Results:

In all, 18 studies met inclusion criteria. A ‘life crisis’ often resulted in a changed need of care, and the transition towards palliative care was sustained by a ‘patient-centered environment’. Family carers described good end-of-life care as providing resident basic care and spiritual support; recognizing and treating symptoms; assuring continuity in care; respecting resident’s end-of-life wishes; offering environmental, emotional and psychosocial support; keeping family informed; promoting family understanding; and establishing a partnership with family carers by involving and guiding them in a shared decision-making. These elements improved the quality of end-of-life of both residents and their family, thus suggesting a common ground between good end-of-life care and palliative care.

Conclusion:

The findings provide a family-driven framework to guide a sensitive and compassionate transition towards palliative care in nursing home.
MicroRNA and their target mRNAs change expression in whole blood of patients after intracerebral hemorrhage
Authors: Cheng Xiyuan , Ander Bradley P , Jickling Glen C , Zhan Xinhua , Hull Heather , Sharp Frank R , Stamova Boryana
Published: April 2019

Previous studies showed changes in mRNA levels in whole blood of rats and humans, and in miRNA in whole blood of rats following intracerebral hemorrhage (ICH). Thus, this study assessed miRNA and their putative mRNA targets in whole blood of humans following ICH. Whole transcriptome profiling identified altered miRNA and mRNA levels in ICH patients compared to matched controls. Target mRNAs of the differentially expressed miRNAs were identified, and functional analysis of the miRNA-mRNA targets was performed. Twenty-nine miRNAs (22 down, 7 up) and 250 target mRNAs (136 up, 114 down), and 7 small nucleolar RNA changed expression after ICH compared to controls (FDR < 0.05, and fold change ≥ |1.2|). These included Let7i, miR-146a-5p, miR210-5p, miR-93-5p, miR-221, miR-874, miR-17-3p, miR-378a-5p, miR-532-5p, mir-4707, miR-4450, mir-1183, Let-7d-3p, miR-3937, miR-4288, miR-4741, miR-92a-1-3p, miR-4514, mir-4658, mir-3689d-1, miR-4760-3p, and mir-3183. Pathway analysis showed regulated miRNAs/mRNAs were associated with toll-like receptor, natural killer cell, focal adhesion, TGF-β, phagosome, JAK-STAT, cytokine–cytokine receptor, chemokine, apoptosis, vascular smooth muscle, and RNA degradation signaling. Many of these pathways have been implicated in ICH. The differentially expressed miRNA and their putative mRNA targets and associated pathways may provide diagnostic biomarkers as well as point to therapeutic targets for ICH treatments in humans.
The brain protective effect of dexmedetomidine during surgery for paediatric patients with congenital heart disease
Authors: Gong Jin , Zhang Rufang , Shen Li , Xie Yewei , Li Xiaobing
Published: April 2019

Objective

To study the brain protective effect of dexmedetomidine (DEX) during surgery in paediatric patients with congenital heart disease (CHD).

Methods

This randomized single-blind controlled study enrolled paediatric patients aged 0–3 years with CHD who underwent surgery and randomized them into two groups: one group received DEX and the control group received 0.9% NaCl during anaesthesia. Demographic data, heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were recorded. Levels of neuron specific enolase (NES) and S-100β protein were determined using enzyme-linked immunosorbent assays.

Results

The study enrolled 80 paediatric patients with CHD. Compared with the control group, HR, MAP and CVP were significantly lower in the DEX group at all time-points except for T0. At all time-points except for T0, the levels of jugular venous oxygen saturation in the DEX group were significantly higher compared with the control group. At all time-points except for T0, the levels of arterial venous difference and cerebral extraction of oxygen were significantly lower in the DEX group compared with the control group. Levels of NES and S-100β protein in the DEX group were significantly lower compared with the control group at all time-points except for T0.

Conclusion

DEX treatment during surgery for CHD improved oxygen metabolism in brain tissues and reduced the levels of NES and S-100β protein.
CytoSorb® hemoadsorption and mechanical circulatory support in a newborn with refractory shock after congenital heart surgery
Authors: Perez Marie-Hélène , Maitre Guillaume , Longchamp David , Amiet Vivianne , Natterer Julia , Ferry Thomas , Schneider Antoine , Plaza Wuthrich Sonia , Di Bernardo Stefano
Published: April 2019

Refractory cardiogenic and vasoplegic shock after congenital heart surgery is a threatening condition leading to high morbidity and mortality. Control of hemodynamic and inflammatory response is fundamental in medical strategy. We report the case of a newborn with cardiogenic and vasoplegic shock secondary to cardiopulmonary bypass for atrioseptostomy and prostaglandin treatment in the context of hypoplastic left heart syndrome, successfully treated with a combination of mechanical circulatory support and cytokine hemoadsorption column (CytoSorb®). Vasopressor support was weaned during the time of treatment without multiple organ failure occurrence. The use of CytoSorb® cartridge inserted in an extra-corporeal circuit even in a newborn is easy and feasible, as long as some precautions are considered. Routine monitoring of drugs levels is mandatory during the use of the cartridge and immediately after.
Working in group therapy during a period of social trauma
Authors: Mitsopoulou-Sonta Lila
Published: April 2019

My experience in working with groups in therapy shows that the individual is inevitably bound to the social. Based on a group of borderline and psychotic patients in a psychiatric hospital, I would like to demonstrate the effects of social trauma (terrorist attack) on the internal life of the group, as well as the different types of transference that we observe in it. The group works with the ‘Photolanguage’ method. Patients have the possibility to put words on their affects, speak about memories and sensations through images that mobilize feelings in a playful manner. The capacity of the group to contain and to transform is precious and promotes the subjective appropriation of difficult affects. Group therapy is important in this type of situation as the diffusion of transference reinforces the capacity of contention in the group. The synergy between the group dynamics and the mediating object offers a field of work on the primitive experiences of each patient and creates a transformation of internal images and representations as the person works on the ‘first psychic material’, which is not elaborated.
Distinct Physiological Mechanisms Induce Latitudinal and Sexual Differences in the Photoperiodic Induction of Diapause in a Fly
Authors: Yamaguchi Koki , Goto Shin G.
Published: April 2019

Many temperate insects enter diapause (dormancy) for overwintering in response to short days (long nights). A latitudinal cline in the critical day lengths for the photoperiodic induction of diapause has been reported in various insect species. However, the physiological mechanisms underlying this cline have remained elusive. We approached this issue in the flesh fly Sarcophaga similis, in which the photoperiodic time measurement system meets the “external coincidence model.” In this model, measuring day lengths depends on whether the photoinducible phase (φi), determined by a circadian clock, is exposed to light or not. First, we detected a clear latitudinal cline in the critical day lengths of flies collected from 4 localities at different latitudes. The phase positions of the φi, which can be verified by night interruption photoperiods, also showed a clear latitudinal cline. This result supports the hypothesis that the latitudinal cline in the critical day length is produced by the difference in the phase positions of the φi among different strains. A sexual difference in the critical day length for photoperiodic induction has also been detected in various species. In this study, a sexual difference in the critical day length was observed in the southern strains but there was no sexual difference in the phase positions of the φi. This result indicates that both sexes measure photoperiods in the same manner. Males are less sensitive than females to the light pulse given at the φi, suggesting a quantitative difference in the photoperiodic time measurement and counter systems. This study clearly reveals that distinct mechanisms induce latitudinal and sexual differences in the critical day length for the photoperiodic induction of diapause in a fly.
Epithelial cell adhesion on films mimicking surface of polymeric scaffolds of artificial urethra compared to molecular modeling of integrin binding
Authors: Kollar Jakub , Morelli Andrea , Chiellini Federica , Miertus Stanislav , Bakos Dusan , Frecer Vladimir
Published: April 2019

In this study, a combined experimental and computational study of long-term human bladder epithelial cell line HBLAK adhesion and proliferation on five different polymeric surfaces, namely hyaluronic acid, amylose, collagen, polyhydroxybutyrate, and polylactic acid, was performed with the goal to understand the nature of the attraction between various surface materials and a simplified model of the cell surface (transmembrane protein integrin). These biodegradable polymers are frequently used as scaffolds for tissue engineering. During formation of the new tissue, the scaffold polymers are gradually replaced by the natural extracellular matrix of the proliferating cells. Cell adhesion and proliferation experiments were carried out employing thin polymer films prepared by solvent casting while for the computational approach three-dimensional molecular models of layers of ordered polymeric fibers were used as quasi-planar nano-sized models of polymeric surface patches. Experimental results indicated a good capability of amylose, polyhydroxybutyrate, and hyaluronic acid polymer films to foster cell adhesion. Proliferation experiment, carried out by incubating cells with the investigated polymer films for 72 h, showed that all the investigated polymers are able to sustain a good proliferation of HBLAK cells almost comparable to plain glass. Computational estimate of molecular mechanic interaction energies between three-dimensional models of polymeric films and the collagen-binding α2 I domain of the cell adhesion receptor integrin α2β1 confirmed elevated affinity to amylose and polyhydroxybutyrate that is related to higher polarity of function groups on the film surface as documented by the maps of molecular electrostatic potential. This combined experimental and modeling approach can contribute to rational design and surface modifications of polymeric material suitable for forming the scaffolds of human urethra that can be effectively colonized by stem cells.
Stimulant Therapy in Acute Traumatic Brain Injury: Prescribing Patterns and Adverse Event Rates at 2 Level 1 Trauma Centers
Authors: Barra Megan E. , Izzy Saef , Sarro-Schwartz Aliyah , Hirschberg Ronald E. , Mazwi Nicole , Edlow Brian L.
Published: April 2019

Background/Objective:

Pharmacological stimulant therapies are routinely administered to promote recovery in patients with subacute and chronic disorders of consciousness (DoC). However, utilization rates and adverse drug event (ADE) rates of stimulant therapies in patients with acute DoC are unknown. We aimed to determine the frequency of stimulant use and associated ADEs in intensive care unit (ICU) patients with acute DoC caused by traumatic brain injury (TBI).

Methods:

We retrospectively identified patients with TBI admitted to the ICU at 2 level 1 trauma centers between 2015 and 2018. Patients were included if they were stimulant naive at baseline and received amantadine, methylphenidate, or modafinil during ICU admission. Stimulant dose reduction or discontinuation during ICU admission was considered a surrogate marker of an ADE. Targeted chart review was performed to identify reasons for dose reduction or discontinuation.

Results:

Forty-eight of 608 patients with TBI received pharmacological stimulant therapy (7.9%) during the study period. Most patients were diagnosed with severe TBI at presentation (60.4%), although stimulants were also administered to patients with moderate (14.6%) and mild (25.0%) TBI. The median time of stimulant initiation was 11 days post-injury (range: 2-28 days). Median Glasgow Coma Scale score at the time of stimulant initiation was 9 (range: 4-15). Amantadine was the most commonly prescribed stimulant (85.4%) followed by modafinil (14.6%). Seven (14.6%) patients required stimulant dose reduction or discontinuation during ICU admission. The most common ADE resulting in therapy modification was delirium/agitation (n = 2), followed by insomnia (n = 1), anxiety (n = 1), and rash (n = 1); the reason for therapy modification was undocumented in 2 patients.

Conclusions:

Pharmacological stimulant therapy is infrequently prescribed but well tolerated in ICU patients with acute TBI at level 1 trauma centers. These retrospective observations provide the basis for prospective studies to evaluate the safety, optimal dose range, and efficacy of stimulant therapies in this population.
Visible and Invisible Social Support: How, Why, and When
Authors: Zee Katherine S. , Bolger Niall
Published: April 2019

Social relationships can be a vital source of help in difficult times. However, attempts to provide social support that is visible—direct and recognized by recipients as help—can sometimes have unintended negative effects. By contrast, invisible support—provided indirectly such that recipients do not interpret the behavior as help—can circumvent potential negative effects. In this article, we synthesize empirical evidence on support visibility using three organizing questions: How do support attempts differ in visibility? Why is invisible support often more beneficial than visible support? When is invisible support, as opposed to visible support, needed? The answers to these questions can illuminate mechanisms of effective support generally, help explain known variability in support outcomes, and stimulate further research.
Patterns of All-Cause Mortality in Papua New Guinea, 2011
Authors: Kitur Urarang , Adair Tim , Lopez Alan D.
Published: April 2019

Existing estimates of mortality for Papua New Guinea (PNG) have primarily been based on models using little empirical data, and without estimation of life expectancy at subnational level. We used data on deaths from the 2000 and 2011 censuses and indirect demographic methods to estimate under-5 mortality (5q0), adult mortality (45q15), and life expectancy by province and sex. A Socioeconomic Composite Index was constructed to assess the plausibility of life expectancy estimates. We generated 5q0 estimates (68 per 1000 live births for males and 58 for females), 45q15 (269 per 1000 for males and 237 for females), and life expectancy (62.0 years for males and 64.3 for females) in PNG in 2011. Provinces with low life expectancy had correspondingly low levels of development as measured by the Composite Index, and vice versa. These subnational estimates of mortality levels and patterns maybe useful at the provincial level to improve population health in PNG.
Introduction to Special Issue: The Legacy of Columbine—Implications for Policy After 20 Years
Authors: Addington Lynn A. , Muschert Glenn W.
Published: April 2019

This introduction provides an overview to the special issue, which marks the twentieth anniversary of the shootings at Columbine High School by considering the effect on policy addressing school violence and mass shootings. We asked each of the contributors to consider changes in their area of interest over the past two decades as well as future research and policy issues. The resulting five contributions take various forms: three are traditional scholarly articles, one is a personal commentary, and one is an afterword that combines a scholarly format with professional reflection. In our introduction, we summarize each one. As each article identifies the need for continued work in this area, and we conclude by providing a few examples of this research.
Moral Distress and Attitudes About Timing Related to Comfort Care for Hospitalized Patients: A Survey of Inpatient Providers and Nurses
Authors: Bender Melissa A. , Andrilla C. Holly A. , Sharma Rashmi K. , Hurd Caroline , Solvang Nicole , Mae-Baldwin Laura
Published: April 2019

Context:

Providing nonbeneficial care at the end of life and delays in initiating comfort care have been associated with provider and nurse moral distress.

Objective:

Evaluate provider and nurse moral distress when using a comfort care order set and attitudes about timing of initiating comfort care for hospitalized patients.

Methods:

Cross-sectional survey of providers (physicians, nurse practitioners, and physician assistants) and nurses at 2 large academic hospitals in 2015. Providers and nurses were surveyed about their experiences providing comfort care in an inpatient setting.

Results:

Two hundred five nurse and 124 provider surveys were analyzed. A greater proportion of nurses compared to providers reported experiencing moral distress “some, most, or all of the time” when using the comfort care order set (40.5% and 19.4%, respectively, P = .002). Over 60% of nurses and providers reported comfort care was generally started too late in a patient’s course, with physician trainees (81.4%), as well as providers (80.9%) and nurses (84.0%) < 5 years from graduating professional school most likely to report that comfort care is generally started too late.

Conclusions:

The majority of providers and nurses reported that comfort care was started too late in a patient’s course. Nurses experienced higher levels of moral distress than providers when caring for patients using a comfort care order set. Further research is needed to determine what is driving this moral distress in order to tailor interventions for nurses and providers.
Domestic Employment: Making Visible an Invisible Relationship
Authors: Masterson Courtney R. , Hoobler Jenny M.
Published: April 2019

Globally, millions of women and men are employed to care for children, adults with physical or mental disabilities, and/or households. The outcomes of paid domestic work go far beyond the private households within which it occurs; yet, this work is most often economically and socially invisible. In this article, we detail the distinct nature of this work by bringing attention to four aspects of domestic employment: physical space, power, purpose, and emotional experiences. We also identify emerging macro-level issues that may help advance our knowledge of workers’ and employers’ experiences. In doing so, we raise questions that may enable scholars, employers, and policy makers alike to better understand and elevate the well-being of millions of workers globally.
Crowdsourcing Qualitative Thematic Analysis
Authors: Hilton Lara G. , Azzam Tarek
Published: April 2019

Evaluations that include stakeholders aim to understand their perspectives and to ensure that their views are represented. This article offers a new approach to gaining stakeholder perspectives through crowdsourcing. We recruited a sample of individuals with chronic low back pain through a crowdsourcing site. This sample coded textual data describing pain, provided themes, and provided feedback on constructs and procedures. The results generated by the crowdsourced participants were compared to results generated by experts. We found that crowdsourcing to develop code and textual responses was feasible, rapid, and inexpensive, offering the potential to enhance patient stakeholder engagement in evaluation. Crowdsourcing has broad implications for evaluation science beyond the health sector.
Polymerase chain reaction analysis of aqueous humor specimens in the diagnosis of cytomegalovirus retinitis in AIDS patients
Authors: Mao Feifei , Sun Huiyu , Li Dan , Wang Shengnan , Lu Dan
Published: April 2019

Purpose:

To determine the value of the polymerase chain reaction analysis of aqueous humor specimens as a tool to diagnose cytomegalovirus retinitis in AIDS patients.

Methods:

In all, 63 AIDS patients were evaluated in this study. They were sorted into two diagnostic categories: eyes with active cytomegalovirus retinitis and eyes without active cytomegalovirus retinitis. The aqueous humor and blood samples were collected and analyzed by polymerase chain reaction.

Results:

A total of 49 patients had active cytomegalovirus retinitis (77.8%) and 14 patients had inactive cytomegalovirus retinitis or normal fundus (22.2%). The mean average of patients was 39 years (range: 22–59). The majority of patients were male (90.5%). Cytomegalovirus DNA was detected in 46 and 7 of 49 aqueous and blood samples, respectively, from AIDS patients with active cytomegalovirus retinitis. We did not detect cytomegalovirus DNA in any of the eyes without active cytomegalovirus retinitis. The sensitivity of polymerase chain reaction in the detection of cytomegalovirus in aqueous humor and blood samples was 93.5% and 14.3%, respectively.

Conclusions:

The polymerase chain reaction analysis is a safe, highly specific, and sensitive method to diagnose cytomegalovirus retinitis.
Components Affecting Pharmaceutical Strategic Purchasing: A Scoping Review
Authors: Bastani Peivand , Ghanbarzadegan Arash , Vatankhah Soudabeh , Samadbeik Mahnaz
Published: April 2019

Pharmaceutical strategic purchasing is considered as a key to improve access to medicines especially for developing countries. The aim of this scoping review is to determine the most important components affecting pharmaceutical strategic purchasing. Here, we employed a comprehensive search strategy across PubMed, ProQuest, EBSCO, ISI Web of Science, Scopus, ScienceDirect, and Google Scholar for the terms related to medicines strategic purchasing. Among 13 included studies, 7 (53.85%) and 6 (46.15%) studies belonged to the developing and developed countries, respectively. Six main variables were emphasized as the effective variables on medicines strategic purchasing, including purchasing interventions, target group and service users, providers and suppliers of interventions, methods and motivations, price, and finally structure and organization. It seems that the insurance organizations of developing countries can achieve strategic purchasing only through the modification of the pharmaceutical pricing system and payment systems. Furthermore, they should pay attention to the real needs of target groups (demand) and modify the structure and organization as well as purchasing the most effective medicines from the best pharmaceutical providers.
Using developmental evaluation principles to build capacity for knowledge mobilisation in health and social care
Authors: Harper Lesley M. , Dickson Rumona
Published: April 2019

This article contributes to Developmental Evaluation practice by highlighting the impact of embedding Developmental Evaluation principles into the learning approach of a capacity building initiative named Evidence for Change. The health and social care teams participating in Evidence for Change were operating within a complex environment requiring radical change to tackle health inequalities and provide modern, cost-effective, evidence-informed, quality of care for all. A gap in the literature around capacity building models for knowledge mobilisation led the authors to explore Developmental Evaluation as a potential approach. Naturally occurring evidence was used to develop Evidence for Change. Questionnaires, focus groups and structured interviews were used to assess the impact. Results demonstrated that Evidence for Change supported evidence-informed practice change and learning for individuals, teams, organisations and local communities. The report concludes that embedding Developmental Evaluation principles into Evidence for Change was instrumental in providing an innovative capacity building model for effective knowledge mobilisation in health and social care.